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Abstract:

Methods, devices, and systems are disclosed for controlled delivery of a
therapy, such as a stimulant, to a mouth of a subject via an oral device
positioned in a secured configuration in the mouth. At least one of a
tongue position stimulator (TST) and tongue position sensor (TSE) is
provided, according to certain aspects. According to another aspect, a
stimulus is delivered to the mouth and/or tongue via a mouthpiece secured
to the subject's teeth. In another regard, a stimulus is delivered that
generates a natural response to eliminate or reduce sleep disorders, such
as for example at least one of snoring and obstructive sleep apnea.

Claims:

1. A tongue position stimulator (TST) system for delivering a stimulant
to stimulate anterior repositioning of a tongue in a mouth of a subject
in order to treat sleep disorder breathing, comprising: an oral device
configured to be secured within the mouth in a secured configuration; a
source of stimulant coupled to the oral device; wherein the oral device
in the secured configuration is configured to deliver the stimulant at an
anterior location at or adjacent to the front incisors within the mouth,
and wherein at least one of (i) the delivery is locally isolated to only
the anterior location, and (ii) the stimulant is configured in a non-gas
preparation for delivery.

2. The system of claim 1, wherein the delivery is locally isolated to
only the anterior location.

3. The system of claim 1, wherein the source of stimulant is configured
in a non-gas preparation for delivery.

4. The system of claim 3, wherein the delivery is locally isolated to
only the anterior location.

5. The system of claim 1, wherein the source of stimulant is located at
an external position outside of the mouth, and further comprising: a
delivery assembly coupled to the source and also to the oral device, and
that is configured to deliver the agent from the source in the external
position to the oral device in the secured configuration.

6. The system of claim 1, further comprising: a reservoir comprising the
source of stimulant; a first delivery port located at a first port
location on the oral device coinciding at or adjacent to an incisor in
the secured configuration; wherein the source of stimulant comprises a
fluid preparation for delivery; and the reservoir is coupled to the first
delivery port for delivery of the fluid stimulant into the mouth at the
first delivery location.

7. The system of claim 6, wherein the first port location coincides at or
adjacent to at least one of the two middle incisors.

8. The system of claim 6, wherein: the reservoir is located externally
from the mouth when the oral device is in the secured configuration; and
a delivery tube is fluidly coupled to the reservoir and also to the
delivery port so as to provide for fluid delivery of the fluid stimulant
from the reservoir to the delivery port.

9. The system of claim 6, wherein: the reservoir is located in the oral
device.

10. The system of claim 1, wherein the system is configured to control a
delivery profile of the stimulant into the mouth via the oral device.

11. The system of claim 10, further comprising: an active controller
comprising a pump coupled to a reservoir containing the stimulant and
that is configured to pump the stimulant according to the controlled
delivery profile into the mouth via the oral device.

12. The system of claim 11, wherein the active controller further
comprises: a software program embedded in a non-transitory computer
readable medium that contains a set of control instructions for
controlling delivery via the pump via a set of input instructions; and a
processor is configured to run the software program to receive the set of
control instructions and control the pump according thereto.

13. The system of claim 12, further comprising: a sensor coupled to the
oral device at a sensor location at or adjacent to the front incisors and
configured to sense information related to a tongue position relative to
the sensor location; and wherein the sensor is further coupled to the
processor and to provide the sensed information as the set of input
instructions.

14. The system of claim 10, wherein the delivery profile comprises a
constant delivery rate of the stimulant over a time period.

15. The system of claim 14, wherein the time period is configured to
coincide with a sleep period for the subject.

16. The system of claim 10, wherein the controlled delivery profile
comprises a changing delivery rate of the therapy over time between at
least a first rate and a second rate that is below the first rate.

17. The system of claim 16, wherein the changing delivery rate comprises
a cycle between the first and second rates over the time.

18. The system of claim 16, wherein the first and second rates comprise
on and off conditions.

19. The system of claim 18, wherein the on and off conditions are
relative to a threshold for achieving a therapeutic result in the
subject, such that the first rate comprising the on condition is above
the threshold, and the second rate comprising the off condition is below
the threshold.

20. The system of claim 18, wherein the second rate comprising the off
condition comprises a substantially zero rate and non-delivery of the
therapy.

21. The system of claim 18, wherein the second rate comprising the off
condition comprises a non-zero rate of delivering the therapy below the
threshold.

22. The system of claim 1, wherein: the oral device comprises a palatal
bridge-less mouthpiece with a dental cavity configured to nest on at
least one tooth in the mouth.

23. The system of claim 1, further comprising: a coating deposited on a
dispensing surface of the oral device at a delivery location and
comprising the source of stimulant; and wherein the coating is configured
to release the stimulant into the mouth at the delivery location.

24. The system of claim 23, wherein the coating is deposited onto the
dispensing surface via an ultraviolet (UV) light linking process.

25. The system of claim 23, wherein the coating is deposited onto the
dispensing surface via a solvent-based deposition.

26. The system of claim 23, and further comprising: a film deposited as a
capsule over the coating and configured to dissolve in the mouth over
sufficient time for the patient to fall asleep before the stimulant
starts to release from the coating into the mouth.

27. The system of claim 26, further comprising: multiple alternating
layers of the coating containing the therapeutic agent and the film,
respectively, and configured to dissolve sequentially over time in the
mouth so as to control a changing delivery profile of the agent over time
in the mouth.

28. The system of claim 27, wherein: the stimulant comprises a taste
stimulant in the alternating coating layers; the alternating film layers
are substantially tasteless: a taste stimulant in the coating; and
wherein the multiple alternating layers are configured to dissolve
sequentially over time so as to control intermittent delivery of the
taste as the alternating layers dissolve in the mouth.

29. The system of claim 1, wherein the stimulant comprises a delivered
energy.

30. The system of claim 1, wherein the stimulant comprises a cryogenic
cooling stimulant.

31. The system of claim 1, wherein the stimulant comprises a material.

32. The system of claim 31, wherein the material comprises a fluid.

33. The system of claim 32, wherein the fluid comprises a liquid.

34. The system of claim 32, wherein the fluid comprises a gas.

35. The system of claim 31, wherein the material comprises a flavor.

36. The system of claim 31, wherein the material comprises a taste.

37. The system of claim 31, wherein the material comprises a smell.

38. The system of claim 31, wherein the material comprises a liquid taste
stimulant.

39. The system of claim 31, wherein the material comprises a sweet taste.

40. The system of claim 39, wherein the sweet taste comprises a sugar, or
a pre-cursor, analog, or derivative thereof.

41. The system of claim 40, wherein the sugar comprises xylitol, or a
pre-cursor, analog, or derivative thereof.

42. The system of claim 1, wherein the stimulant comprises a mechanical
stimulant.

43. The system of claim 1, wherein the stimulant comprises a texture
stimulant.

44. A tongue position stimulator (TST) method for delivering a stimulant
to stimulate anterior repositioning of a tongue in a mouth of a subject
in order to treat sleep disorder breathing, comprising: securing an oral
device within the mouth in a secured configuration; coupling a source of
stimulant to the oral device; delivering the stimulant at an anterior
location at or adjacent to the front incisors within the mouth via the
oral device in the secured configuration; and at least one of (i) locally
delivering the stimulant to only the anterior location, and (ii)
delivering the stimulant in a non-gas preparation.

45. The method of claim 44, further comprising: locally delivering the
stimulant to only the anterior location.

46. The method of claim 44, further comprising: delivering the stimulant
in a non-gas preparation.

47. The method of claim 45, further comprising: locally delivering the
stimulant to only the anterior location.

48. The method of claim 44, further comprising: positioning the source of
stimulant at an external position outside of the mouth; coupling a
delivery assembly to the source and also to the oral device, and
delivering the stimulant from the source in the external position to the
oral device in the secured configuration.

49. The method of claim 44, further comprising: providing the stimulant
in a fluid delivery preparation; storing the source of stimulant in a
reservoir; fluidly coupling the source to a first delivery port located
at a first port location on the oral device coinciding at or adjacent to
an incisor in the secured configuration; delivering the fluid stimulant
from the reservoir to the first delivery port for delivery of the fluid
stimulant into the mouth at the first delivery location.

50. The method of claim 49, further comprising: positioning the first
port location to coincide at or adjacent to at least one of the two
middle incisors.

51. The method of claim 49, further comprising: positioning the reservoir
externally from the mouth when the oral device is in the secured
configuration; and fluidly coupling a delivery tube to the reservoir and
also to the delivery port so as to provide for fluid delivery of the
fluid material from the reservoir to the delivery port.

52. The method of claim 49, further comprising: positioning the reservoir
in the oral device.

53. The method of claim 44, further comprising: controlling a delivery
profile of the stimulant into the mouth via the oral device.

54. The method of claim 53, further comprising: actively controlling the
delivery profile using a pump coupled to a reservoir containing the
stimulant; and pumping the stimulant according to the controlled delivery
profile into the mouth via the oral device.

55. The method of claim 54, wherein the active controlling further
comprises: using a processor to run a software program embedded in a
non-transitory computer readable medium to generate a set of control
instructions from the software program in response to a set of input
instructions received by the processor; and controlling delivery of the
stimulant via the pump via the set of control instructions.

56. The method of claim 55, further comprising: coupling a sensor to the
oral device at a sensor location at or adjacent to the front incisors;
sensing information related to a tongue position relative to the sensor
location via the sensor; and coupling the sensor to the processor to
provide the sensed information as the set of input instructions.

57. The method of claim 53, further comprising: controlling the delivery
profile according to a constant delivery rate of the stimulant over a
time period.

58. The method of claim 57, further comprising: configuring the time
period to coincide with a sleep period for the subject.

59. The method of claim 53, further comprising: controlling the delivery
profile according to a changing delivery rate of the therapy over time
between at least a first rate and a second rate that is below the first
rate.

60. The method of claim 59, further comprising: cycling the changing
delivery rate between the first and second rates over the time period.

61. The method of claim 59, wherein the first and second rates comprise
on and off conditions.

62. The method of claim 61, wherein the on and off conditions are
relative to a threshold for achieving a therapeutic result in the
subject, such that the first rate comprising the on condition is above
the threshold, and the second rate comprising the off condition is below
the threshold.

63. The method of claim 61, wherein the second rate comprising the off
condition comprises a substantially zero rate and non-delivery of the
therapy.

64. The method of claim 61, wherein the second rate comprising the off
condition comprises a non-zero rate of delivering the therapy below the
threshold.

65. The method of claim 44, further comprising: providing the oral device
as a palatal bridge-less mouthpiece with a dental cavity; and nesting the
dental cavity on at least one tooth in the mouth.

66. The method of claim 44, further comprising: depositing a coating
comprising the source of stimulant on a dispensing surface at a delivery
location on the oral device; and releasing the stimulant into the mouth
at the delivery location via the coating.

68. The method of claim 66, further comprising: depositing the coating
onto the dispensing surface via a solvent-based deposition.

69. The method of claim 66, and further comprising: encapsulating the
coating with a film configured to dissolve in the mouth over sufficient
time for the patient to fall asleep before the stimulant starts to
release from the coating into the mouth.

70. The method of claim 69, further comprising: depositing multiple
alternating layers of the coating containing the therapeutic agent and
the film, respectively; and dissolving the alternating layers
sequentially over time in the mouth so as to control a changing delivery
profile of the agent over time in the mouth.

71. The method of claim 70, wherein: the stimulant comprises a taste
stimulant and the alternating film layers are substantially tasteless in
the alternate layers, respectively, and further comprising: sequentially
dissolving the multiple alternating layers over time so as to control
intermittent delivery of the taste as the alternating layers dissolve in
the mouth.

72. The method of claim 44, wherein the stimulant comprises a delivered
energy.

82. The method of claim 74, wherein the material comprises a sweet taste.

83. The method of claim 82, wherein the sweet taste comprises a sugar, or
a pre-cursor, analog, or derivative thereof.

84. The method of claim 83, wherein the sugar comprises xylitol, or a
pre-cursor, analog, or derivative thereof.

85. The method of claim 44, wherein the stimulant comprises a mechanical
stimulant.

86. The method of claim 44, wherein the stimulant comprises a texture
stimulant.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. patent
application Ser. No. 13/649,967 filed on Oct. 11, 2012, incorporated
herein by reference in its entirety. U.S. patent application Ser. No.
13/649,967 filed on Oct. 11, 2012 is a nonprovisional of U.S. provisional
patent application Ser. No. 61/603,671 filed on Feb. 27, 2012,
incorporated herein by reference in its entirety, a nonprovisional of
U.S. provisional patent application Ser. No. 61/551,927 filed on Oct. 27,
2011, incorporated herein by reference in its entirety, and a 35 U.S.C.
§111(a) continuation-in-part of PCT international application number
PCT/US2012/037392 filed on May 10, 2012, incorporated herein by reference
in its entirety. PCT international application number PCT/US2012/037392
filed on May 10, 2012 is a nonprovisional of U.S. provisional patent
application Ser. No. 61/603,671 filed on Feb. 27, 2012, incorporated
herein by reference in its entirety, and a nonprovisional of U.S.
provisional patent application Ser. No. 61/484,520 filed on May 10, 2011,
incorporated herein by reference in its entirety. This application is a
nonprovisional of U.S. provisional patent application Ser. No. 61/603,671
filed on Feb. 27, 2012, incorporated herein by reference in its entirety.
Priority is claimed to each of the foregoing applications.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

[0002] Not applicable

INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A COMPACT DISC

[0003] Not Applicable

NOTICE OF MATERIAL SUBJECT TO COPYRIGHT PROTECTION

[0004] A portion of the material in this patent document is subject to
copyright protection under the copyright laws of the United States and of
other countries. The owner of the copyright rights has no objection to
the facsimile reproduction by anyone of the patent document or the patent
disclosure, as it appears in the United States Patent and Trademark
Office publicly available file or records, but otherwise reserves all
copyright rights whatsoever. The copyright owner does not hereby waive
any of its rights to have this patent document maintained in secrecy,
including without limitation its rights pursuant to 37 C.F.R. §1.14.

BACKGROUND OF THE INVENTION

[0005] 1. Field of the Invention

[0006] The present disclosure relates to methods, devices, and/or systems
for delivering therapies and sensing biologic activities via oral
appliances in the mouth, in particular for stimulating and sensing tongue
activity during sleep, and including in particular for treating sleep
disorder breathing, including but not limited conditions of obstructive
sleep apnea, snoring, or mild sleep apnea.

[0007] 2. Background and Description of Related Art

[0008] Snoring, which is very common among humans, is a noise produced
while breathing during sleep as a result of certain conditions within the
body. In most cases, snoring results from vibration of the soft palate
and uvula. Snoring often involves a displacement of the tongue from its
rest position as well as breathing through the mouth resulting from the
abnormal positioning and functioning of the tongue. Snoring can be
reduced if the tongue is drawn forward to a more normal position (e.g.,
in contact with the anatomical folds or wrinkles (rugae) or the mucosa of
the anterior palatal region of the mouth. When in an abnormal position,
the tongue leaves a space for the passage of air between the hard palate
and the top of the tongue and over the soft palate. The passage of air
over the soft palate can cause vibrations which are the source behind the
snoring sound.

[0009] While some degree of snoring is tolerable and has no significant
adverse consequence, a common problem is that, on its own, snoring can
disturb the sleep of others near the snoring individual. As a result,
snoring can result in a diminished ability to remain attentive on both
the individual snoring as well as others whose sleep might be adversely
affected by the snoring party. As a result, even moderate snoring can
result in a reduction in work efficiency and lead to a higher risk of
industrial and driving accidents.

[0010] A more serious sleep disorder can result from symptomatic, repeated
upper airway obstruction during sleep, commonly referred to as
Obstructive Sleep Apnea (OSA). "Apnea" is a Greek word meaning without
breath. Individual suffering from sleep apnea literally stop breathing in
their sleep. It is not uncommon for the incidence of apnea events to
occur hundreds of times during the night.

[0011] In a given night, the number of involuntary breathing pauses or
"apneic events" could be as high as 20 to 60 or more per hour. These
breathing pauses are almost always accompanied by snoring between apnea
episodes. Sleep apnea can also be characterized by choking sensations.
Ingestion of alcohol and sleeping pills increases the frequency and
duration of breathing pauses in people with sleep apnea.

[0012] 30-40% of OSA patients cannot tolerate first-line treatment (such
as continuous positive airway pressure, CPAP. Accordingly individuals may
consider other options including oral appliances and surgery. Mandibular
repositioning appliances and surgery can offer benefit for selected
patients, but such conventional remedies can carry risks such as
temporomandibular joint disturbance, changes in dental occlusion, or
tooth pain for the former and a wide spectrum of potential complications
that includes dysphagia or serious perioperative events including
myocardial infarction and death in the latter.

[0013] The importance of the tongue in OSA and snoring has been recognized
for 30 years, as evidenced by the numerous attempts designed to prevent
the tongue from falling backwards or to move it forward actively or
passively. Oral appliances and multiple tongue-directed surgeries show
some promise, but these remedies carry significant risks and side
effects, in addition to potential significant bleeding and impairments of
taste, swallowing, or speech. Because of the limitations of available
passive treatments, active tongue neuromuscular stimulation techniques
were attempted to implant wire electrodes, surface stimulating electrodes
and hypoglossal nerve stimulation.

[0014] A number of factors contribute to OSA, including dilator muscle
activation, pharyngeal anatomy, lung volume, arousal threshold, and
ventilatory control, with the former two playing critical roles for most
individuals. Upper airway patency relies on pharyngeal dilator muscle
tone and changes in lung volume that counteract collapsing forces,
principally intraluminal negative pressure generated during inspiration
and anatomical narrowing of the airway. Individuals with OSA maintain
pharyngeal patency with greater dilator muscle tone (principally
demonstrated in the genioglossus muscle, the primary muscle within the
tongue) during wakefulness; however, sleep onset results in marked
decreases in muscle tone due to the loss of the wakefulness stimulus, in
addition to decreases in negative pressure reflex activity and lung
volume. The effect of decreased muscle tone is magnified in the presence
of tongue enlargement, an anatomical abnormality often seen in OSA,
perhaps related to an increase in fat deposition within the tongue base
in individuals with greater body mass index.

[0015] Additional risk factors for sleep apnea include a family history of
sleep apnea, excess weight, a large neck, a recessed chin, male gender,
abnormalities in the structure of the upper airway, smoking, and alcohol
use. Yet sleep apnea can affect both males and females of all ages,
including children and any weight. Sleep apnea disturbs normal sleep
patterns and people with sleep apnea often feel very sleepy during the
day and their concentration and daytime performance suffer. The
consequences of sleep apnea range from annoying to life-threatening. They
include symptoms suggesting depression, irritability, sexual dysfunction,
learning and memory difficulties, and falling asleep while at work, on
the phone, or driving.

[0017] Untreated sleep apnea patients are 3 times (or more) likely to have
automobile accidents. It has been estimated that up to 50 percent of
sleep apnea patients have high blood pressure. It has recently been shown
that sleep apnea contributes to high blood pressure and other
cardiovascular disease. Risk for heart attack and stroke may also
increase in those with sleep apnea. Sleep apnea is a common disorder that
affects millions of men, women and children and is often undiagnosed. It
is estimated that at least ten million Americans have unrecognized sleep
apnea

[0018] Polysomnography is a test that records a variety of body functions
during sleep, such as the electrical activity of the brain, eye movement,
muscle activity, heart rate, respiratory effort, air flow, and blood
oxygen levels. These tests are used both to diagnose sleep apnea and to
determine its severity. The specific therapy for sleep apnea is tailored
to the individual patient based on medical history, physical examination,
and the results of polysomnography. Traditionally, a therapy for sleep
apnea is tailored to the individual patient based on medical history,
physical examination, and the results of polysomnography.

[0019] Medications are generally not effective in the treatment of sleep
apnea. While oxygen is sometimes used in patients with central apnea
caused by heart failure, it is not used to treat obstructive sleep apnea.
Some of the therapies include the use of Provent®, Breatherite®
strip, Oral appliances that advance the mandible, continuous positive
airway pressure (CPAP), or maxillomandibular advancement surgery, etc.
However, some therapies may be partially or completely ineffective in
addressing both snoring and/or OSA.

[0020] Recently Inspire Medical, Imthera Medical, Apnex Medical and others
have been exploring ways of stimulating tongue, tongue muscle or nerves
that control the tongue by implanting electrodes in the tongue to deliver
electrical signals for stimulation. However, titrating safe levels of
stimulation that does not disturb sleep for each patient is a challenge.
Others have explored ways of stimulating the tongue base by making the
patients wear oral devices. The challenge has been the same.

[0021] Given the limitations of current therapies, there is an enormous
unmet need for effective, well-tolerated, safe, and minimally invasive
OSA treatments. There also remains a need for reducing the incidence of
snoring and/or sleep apena that does not require significant physical
and/or surgical intervention on the patient. In the article, "Impaired
swallowing reflex in patients with obstructive sleep apnea syndrome"
(CHEST 1999; 116:17-21), Teramoto et al. published their findings that
twenty (20) patients with obstructive sleep apnea also had a compromised
swallowing function due to reduced upper airway muscle functions. From
this study, one can conclude that increasing the swallowing frequency
during sleep could result in increased upper airway muscle functions, and
thus potentially reduce or eliminate snoring and obstructive sleep apnea.

[0022] In view of the above, there remains a need for an effective, safe,
and noninvasive device, for use by itself or during administration of
CPAP. The devices, methods and procedures described herein induce a
biological response within a mouth, such as promoting tongue
neuromuscular activation and anterior tongue displacement to reduce
airway obstruction. Additional variations of methods, devices, and
systems described herein can also increase salivation and reduce or
eliminate snoring and obstructive sleep apnea by one or more of the
following: stimulating swallowing, improving muscle tone and increasing
frequency of swallowing.

BRIEF SUMMARY OF THE INVENTION

[0023] Stimulation of swallowing can be achieved in several ways:
stimulation by taste, stimulation by smell and stimulation by mechanical
effect that helps trigger the swallowing reflex. To achieve stimulation,
an interface to the user is provided that allows for delivery of the
stimulus in a beneficial way. Variations of the methods and devices can
include the use of a stimulation appliance delivers one or more stimuli
to the nose, tongue, and/or mouth to induce the effects described above.
For example, variations of the stimulation appliance can include a
mouthpiece, mask and/or one or more tubes placed within or in proximity
to the mouth or nose.

[0024] In the cases of taste and smell stimuli, the stimulation appliance
incorporates a reservoir that allows for delivery of the stimulus over
the sleep period. It is important that delivery of the stimulus be
controlled to achieve efficient stimulation of swallowing, without
causing habituation or arousing involuntary reflexes, such as gagging.
The stimulation appliance comprises means to deliver and regulate the
stimulus, such as an infusion pump. Delivery of the stimulus can be
continuous or intermittent. For intermittent delivery the periods between
delivery of the stimulus can either be regular or variable. Delivery of
stimuli can be regulated by time or by responding to physiological
measurements that are related to the condition being treated, such as air
flow measured at the nostrils, chest cavity movement, pulse or brain
waves. One or more stimuli can be delivered simultaneously or
sequentially during a treatment or regimen. The stimulation appliance can
incorporate elements that further enhance interaction of the user with
the stimulus. The stimulation appliance elements are aimed to encourage
interaction of the user with the stimulation appliance, such as, tongue
movement, mouth movement and stimulating swallowing. These stimulation
appliance elements can be chewable, lickable, or suckable and configured
to fit comfortably in the user's mouth, in proximity to the tongue, such
as roller balls, sponges and suckers. The stimulation elements can be
smooth or incorporate a texture and have a rigid or soft consistency.

[0025] In one variation, the methods and devices described herein are
intended to prevent or reduce habituation as a result of applying the
stimulant or stimulus. Habituation could eventually lessen the effect of
the methods and devices as the individual's response to the stimulus
could decrease as a result of repeated application of the
stimulus/stimulant.

[0026] Accordingly, intermittent delivery of the stimulus/stimulant could
produce a greater stimulating effect. In some variations, random or
apparently/seemingly random, on/off application of the stimulant/stimulus
could improve effectiveness of the methods and/or devices.

[0027] The stimulation can be used as a stand-alone therapy or as an
adjunct to other sleep disturbance therapies, such as CPAP. For example,
a CPAP mask can incorporate a taste or smell stimulation appliance to
deliver a regimen that enhances the response to CPAP in users that
typically are poor or moderate responders of the CPAP therapy. Using an
aerosol of liquid may be introduced with humidification or through
separate tubing. This can be continuous or intermittent. Additional
modification to the mask can be made to allow for mouth retainer or oral
appliance, connected or separate from the CPAP or BiPAP mask that allows
for aerosol or fluid to be released into the mouth either continuously or
intermittently. To avoid continuous release and potential for habituation
to the stimulus, release can be timed to respiration, apnea events or
apnea cycles, timed with respirations, respiratory effort, respiratory
flow, hypoxia, hypopnea, and or oxygen saturations. Further it can be
used as a screening device for assessing tongue obstruction. Since
several anatomical components can contribute to a person's degree of
obstructive sleep apnea, identifying the causes is paramount in
developing a treatment. Using taste stimulation as a non invasive
evaluation of the tongue has the potential to better stratify and
identify patients that have tongue obstruction as a significant component
of their sleep apnea. This is a functional evaluation giving more
information than just relative tongue size or position. This could safely
and cost effectively screen for more invasive procedures like surgery or
implants that reposition or stimulate the tongue.

[0028] The stimulation can be delivered through a typical mouthpiece or
mask made out of rigid or flexible plastics such acrylic, silicone, EVA,
PET, polyethylene, SEBS, polyurethane, polypropylene, PVC material. The
device can be manufactured using typical plastics processing methods,
such as thermoforming, injection molding, transfer molding, liquid
injection molding, overmolding, and the like. The device can be preformed
using standard plastic processes and custom fit to the user in a
secondary processing step. The stimulant is released in a controlled
fashion to increase salivation. In one embodiment, a solution of a taste
compound made from Xylitol or saline is placed in the stimulation
appliance that comprises a delivery pump. The delivery pump can be
programmed to deliver solution in a continuous or intermittent fashion
during the sleep cycle. The solution is delivered from the pump to the
mouthpiece or mask via connecting tubing while the user is asleep as
discussed below. Alternatively, a miniature pump and reservoir can be
incorporated within the mouthpiece or mask. The solution is delivered
during the sleep period to stimulate swallowing, without causing arousals
that awaken the user or elicit an involuntary reflex, such as gagging.
For example, the solution can be delivered at rates of (0.01 to 0.2
ml/min). The solution is made up of Xylitol with concentration in the
range of 2 to 10 Molar. As a result of the taste compound delivery
regimen, the frequency of apneas in a user diagnosed with sleep apnea is
reduced 20-40%. The stimulant could also be combined with a texture, for
example, a dissolvable flavored sponge that draws the tongue because of
taste and tactile sensation. The stimulant could also be a roller, like
the roller discussed below, track ball, or other similar structure. In
any case, a physical stimulant could be used, alone or in combination
with other stimulants, to draw the tongue into a desired position.

[0029] Another variation of the methods and devices includes constant or
near constant delivery of the stimulant but diluting or adjusting the
stimulant so that the response is insufficient to wake the individual.
For example, in cases where the stimulant is a taste stimulant, the
stimulant can be diluted in a solution where the concentration is held
high enough to cause the desired response but low enough to avoid waking
the patient and is continuously delivered over a period of time.

[0030] The methods described herein are intended for treating sleep
disorder breathing in a sleeping individual. In one example the method
includes providing a stimulant that induces at least one natural response
within a mouth of the sleeping individual when the stimulant enters the
mouth; delivering the stimulant at a location behind one or more teeth in
the mouth to induce at least one natural response to reduce sleep
disorder breathing and improve the ability of the sleeping individual to
maintain a sleep state; and intermittently pausing delivery of the
stimulant to temporarily cease inducing the at least one natural
response, where intermittently pausing delivery prevents the stimulant
from waking the individual.

[0031] The method can include automatically delivering the stimulant from
a supply source while the individual is in a sleep state. The natural
response can comprise an activity selected from the group consisting of
salivation, forward movement of the tongue, repositioning of the tongue,
swallowing and a combination thereof. At least one of the activities
described herein can optionally reduce vibrations of a soft palate or
uvula without waking the individual.

[0032] The oral appliance can be a mandibular advancement device, a custom
molded mouthpiece, a continuous positive airway pressure device, a
mouthguard, and a retainer.

[0033] In some variations, the oral appliance comprises an internal
reservoir fluidly coupled to the delivery port, the internal reservoir
containing at least a portion of the stimulant, and where the delivery
port comprises a valve, where providing the stimulant comprises opening
of the valve to dispense the stimulant. Alternatively, or in combination,
the device can include an external reservoir containing the stimulant.

[0034] The stimulant can also trigger an olfactory response in the
individual. Alternatively, or in combination, the devices and methods can
include a second stimulant to trigger an olfactory response in the
sleeping individual.

[0035] In some variations, intermittently pausing delivery of the
stimulant comprises pausing the stimulant until a triggering signal
restarts delivery of the stimulant. Additionally, the devices and methods
can include a dispensing unit in electrical communication with a sensor,
where the triggering signal is generated in response to the sensor.

[0036] Sensors can include a pressure sensor, an optical sensor, a sound
sensor, a movement sensor, an electro-magnetic sensor. In one variation,
the sensor is positioned in the mouth and generates a signal based on a
movement/position of the tongue, or a position/movement of a jaw.
Furthermore, the amount of stimulant delivered can be determined by the
triggering signal. For instance the method and/or device can measure a
degree of tongue movement with the sensor and use the triggering signal
to determine the amount of stimulant based on the degree of movement.

[0037] In another variation, delivering the stimulant and intermittently
pausing delivery of the stimulant are timed with an event selected from a
group consisting of respiration, respiratory effect, respiratory flow,
hypoxia, hypopnea, oxygen saturation, pausing the stimulant until a
triggering signal restarts delivery of the stimulant.

[0038] Another variation of the method includes a method for minimizing
sleep disturbances in an individual during a state of sleep. In one
example, such a method includes positioning a dispensing unit within a
mouth of the individual, where the dispensing unit comprises at least one
port adjacent to a tongue; providing a supply of a stimulant through the
port that induces a biological response in the mouth of the individual
when the stimulant contacts an anterior surface of the tongue;
controlling delivery of the stimulant between a delivery phase, in which
the stimulant is delivered to the mouth to induce the biological response
and a dwell phase, during which delivery of the stimulant to the mouth is
stopped, where controlling delivery of the stimulant permits periodically
inducing the biological response without waking the individual.

[0039] In another variation, the present disclosure includes an oral
device for dispensing a stimulant that produces a biological response
within the mouth to reduce incidents sleep disorder breathing in an
individual. Such a device can include a device body having a dental
cavity for removably nesting with one or more structures within the
mouth; a dispensing port adjacent to an anterior portion of the dental
cavity, such that when the device body is positioned within a mouth the
dental cavity is adjacent to the teeth and the dispensing port is
adjacent to a posterior surface of teeth such that the stimulant leaving
the dispensing port draws the tongue adjacent or next to the posterior
surface of the teeth; a fluid reservoir fluidly coupled to the dispensing
port being configured to maintain a supply of the stimulant; a valve
located in a fluid path between the fluid reservoir and the dispensing
port where the valve allows for intermittent dispensing of the stimulant
through the dispensing port. Regardless of location of placement, the
valve allows for metering or preferential dispensing of the stimulant.

[0040] A variation of the oral device can further include a palatial
nesting section adjacent to the dental cavity and configured to nest
within an arch of a palate to improve retention of the device body within
the mouth.

[0041] In alternative embodiments, stimulants can be made in the form of
capsules or films that dissolve over time. The capsule or film may be
configured such that it gives enough time for the patient to fall asleep
before the stimulant starts to come out of the capsule. The capsule can
be incorporated into a stimulus appliance that the patient wears, such as
mouthpiece, at night. As the patient falls asleep, the capsule starts to
dissolve in the mouth and the taste compound starts to leach out of the
capsule causing the patient to salivate more.

[0042] The capsule may incorporate multiple alternating layers of the
taste compound and tasteless transition layers so that intermittent
delivery of the taste is accomplished as the alternating layers dissolve.

[0043] Another variation of an oral device according to the principles
disclosed herein includes a device for producing a biological response
within the mouth to reduce sleep disorder breathing having a device body
having a dental cavity for removably nesting with one or more structures
within the mouth; and a dispensing surface adjacent to an anterior
portion of the dental cavity, such that when the device body is
positioned within a mouth the dental cavity is adjacent to the teeth and
the dispensing surface is adjacent to a posterior surface of the teeth,
where the dispensing surface comprises a supply of a stimulant, where the
stimulant is releasable from the dispensing surface over a period of time
and draws a tongue adjacent to or next to the posterior surface of the
teeth. Such a device can include the stimulants described herein that are
deposited as coatings on or into the dispensing surface via a process
such as UV-linking, solvent-based deposition, or any such commercially
available procedure.

[0044] Some benefits of the present devices, systems and methods include
safety and comfort, increases muscle tone of the upper airway, the
ability to distribute in an over-the-counter fashion; reduced cost as
compared to many of the existing remedies and over-the-counter sleep
therapy modalities; ease of use; reversible nature of the produce;
non-invasive. Additional benefits include the ability for the tongue to
move freely and to allow for swallowing. Other possible uses for the
devices and methods described herein include treatments for oral hygiene,
xerostomia, nocturnal bruxism, and/or nocturnal gastroesophogeal reflux.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S)

[0045] FIG. 1 depicts a cross sectional view of the upper respiratory
tract in a patient having a blocked airway.

[0046] FIGS. 2A and 2B illustrate variations of an oral device that can be
used to induce a biological response within a mouth of an individual to
reduce the frequency or prevent snoring and/or sleep apnea.

[0047] FIGS. 3A and 3B show phantom views of the oral cavity to illustrate
examples of positioning an oral device within a mouth.

[0049] FIGS. 4A and 4B illustrate a condition immediately prior to
contemporaneous to dispensing a stimulant where an individual is sleeping
and the tongue is in a retracted position causing restriction of the
airway and inability of air to pass through the upper respiratory tract.

[0055]FIG. 7c shows yet another variation of a dispensing device in which
the device comprises a stimulant coupled to a solution so that the
stimulant can be diluted.

[0056] FIG. 8A illustrates one example of a fiberoptic pressure sensor for
use in a variation of an oral appliance as described herein.

[0057] FIGS. 8B and 8C show data from a trial using a variation of a
device; FIG. 8B shows a chart for an apnea-hypopnea index (AHI) results
for individuals with mild to moderate OSA, while FIG. 8B presents the
apnea-hypopnea index (AHI) results for individuals with severe OSA.

[0058]FIG. 9 shows the cTST-TSE system according to one aspect of the
disclosure, with certain components shown schematically for simplicity of
illustration.

[0059]FIG. 10 shows a graph of certain sensed anterior tongue pressure
data recorded versus time under the experiment of Example 2, and reflects
an example comparing time periods of varied ON/OFF states of therapy
delivery.

[0060]FIG. 11 also shows another graph of other sensed anterior tongue
pressure that was recorded vs. time, also under the experimental study of
Example 2, but according to another example showing a period of OFF
delivery condition only.

[0061]FIG. 12 shows another bar graph of frequency of sensed anterior
protective tongue positioning events (per second) vs. time (consecutive
nights over 14 day period), also according to the Example 2 experimental
protocol, but according to another aspect of the study observing results
of using the same stimulus delivery rates and intervals on four separate
nights throughout the 14 day trial.

[0062]FIG. 13 shows a bar graph of the same results featured in FIG. 12,
per frequency of sensed anterior tongue positioning events (per second)
vs. time (consecutive nights over the 14 day period, in split-night
view), but showing comparison results between the first half and the
second half of the nights featured in the graph (i.e. "split night" view
or analysis).

[0063]FIG. 14 shows another bar graph of experimental results of Example
2 according to frequency of sensed anterior protective tongue
repositioning events (per second) vs. time (consecutive nights over 14
day period), but showing results of using a shorter interval than the
pilot trial protocol with various rates.

[0064]FIG. 15 also shows a bar graph of the same results per frequency of
sensed anterior protective tongue repositioning activity events (per
second) vs. time (consecutive nights over 14 day period) shown in FIG.
14, but shows comparison results between the first half and the second
half (when available) of the nights in split night analysis.

[0065]FIG. 16 also shows a bar graph of frequency of sensed anterior
protective tongue repositioning activity events (per second) vs. time
(consecutive nights over 14 day period) but shows results of another
sub-protocol during continuous flow, with no pauses in delivery of
xylitol, but comparing two different stimulant delivery rates.

[0066] FIG. 17 shows an x-y plot of sensed tongue movement to the
protective anterior position as a function of varying stimulant delivery
rates over the experimental design of Example 2.

[0067]FIG. 18 also shows another bar graph reflecting sensed anterior
tongue repositioning events over the 14 days of consecutive treatment at
various rates and protocols of the Example 2 experiment.

[0069] FIG. 1 depicts a cross sectional view of the upper respiratory
tract in a patient having a blocked airway 10. As discussed above,
snoring occurs as a result of vibration of the soft palate 14 and uvula
16 that are located at the end of the hard palate 18. As illustrated, the
tongue 12 is moved from its rest position in a rearward direction causing
impingement of the airway 10 by the rear portion of the tongue 12 against
the uvula 16. As a result, the blockage prevents air, whether breathed
through the mouth or nose 20, from passing through the airway 10 and
ultimately into the throat 24. As shown by arrows 30, the abnormal
position of the tongue 12 prevents passage of air in the nasal cavity 22.
As noted above, this situation leaves a space for the passage of air
between the hard palate and the top of the tongue and over the soft
palate. The passage of air over the soft palate can cause vibrations
which are the source behind the snoring sound as well as contribute to
sleep apnea.

[0070] The devices, methods, and systems described herein can ameliorate
or prevent snoring and/or blockage of the airway 10 leading to improved
sleep quality in an individual. Such devices, methods and system deliver
one or more stimuli to the sleeping individual to induce a natural or
biological response within the body that lessens snoring and/or opens the
airway to minimize the incidence of apnea. In most variations of the
devices, methods and systems, the stimuli (or the delivery rate of the
stimuli) should induce the natural response at an effective level that
does not wake the individual. However, alternate variations may include
delivering the stimuli with the intent to wake the individual.

[0071]FIG. 2A illustrates one variation of an oral device 100 that can be
used to induce a biological response within a mouth of an individual to
reduce the frequency or prevent snoring and/or sleep apnea. In this
variation, the oral device 100 includes a device body 102 having a dental
cavity 104 for nesting the device on one or more teeth of the individual.
While the illustrated variation shows the device body 102 having a dental
cavity 104 that accommodates a number of teeth, variations of the device
100 include a dental cavity 104 that is suited for nesting the device 100
on one or more teeth. Alternate variations can include oral devices 100
that nest directly on the palate, gums, or beneath the tongue.
Accordingly, such variations need not include a dental cavity.

[0072] The illustrated oral device 100 also includes a dispensing port 106
that can be used to deliver a stimulant to the oral cavity, mouth and/or
tongue. In this variation, the port 106 is coupled to a supply of the
stimulus via a tube 108 that forms a part of a fluid path between the
supply or reservoir of the stimulus and the port 106. The tube 108
includes a fitting to allow for coupling to an external reservoir. As
described in further detail below, a valve (shown in FIG. 2B) is located
between the port 106 and the reservoir. The valve allows for intermittent
dispensing of the stimulant through the dispensing port 106. In some
cases a valve is not required. Instead, the device uses a pressure
differential to drive the stimulant through the port.

[0073]FIG. 2B illustrates another variation of an oral device 100 for use
as described herein. In this variation the device 100 also includes a
dispensing port 106 used to deliver a stimulant to the oral cavity, mouth
and/or tongue. However, in this variation, the port 106 is coupled to a
supply or reservoir 110 that is directly coupled to a body 102 of oral
device 100. The reservoir 110 is in fluid communication with the port 106
such that a fluid path is formed therebetween. FIG. 2B also shows a valve
112 located adjacent to the port 106 where the valve allows for
intermittent dispensing of the stimulant through the dispensing port 106.
In alternative variations, the valve can be placed anywhere in or around
the lumen or fluid path. This variation of the device 100 is a wholly
self contained oral device that can rely on internal circuitry to
dispense the stimulant and/or rely on an external unit (not shown) that
can wirelessly transmit a triggering signal to the valve 112 to dispense
the stimulant. The dispensing conditions and frequency are described
below. The variation of the oral device 100 shown in FIG. 2B can be
disposable after depletion of the stimulus or can have a second refill
valve 114 to permit the user to replenish the stimulant as required.

[0074] FIGS. 3A and 3B show phantom views of the oral cavity to illustrate
some examples of positioning one or more oral devices 100 can be placed
to produce the natural response that reduces snoring and/or sleep apnea.
As illustrated, the oral device 100 can be positioned or nested to one or
more teeth 8. In alternate variations, the device 100 can be nested or
temporarily affixed to gums, a palate, or other structure within the
mouth. FIG. 3A shows nesting of the device 100 on the top front teeth 8
while FIG. 3B illustrates nesting of the device 100 on the bottom front
teeth 8. However, alternate devices 100 permits removable nesting of the
device with one or more structures within the mouth, including the side
teeth, or other structures within the mouth. Additionally, the dispensing
port 106 can be positioned anywhere on the device. However, the
illustrated variation shows a dispensing port 106 adjacent to an anterior
portion of the dental cavity or device body. With this positioning the
dental cavity is adjacent to the teeth. Such positioning allows the
dispensing port 106 to deliver the stimulant 122 and draw the tongue 12
to a desired position in the mouth. FIGS. 3A and 3B illustrate oral
devices 100 that are coupled to external reservoirs 120 that can
optionally include one or more controllers or other dispensing unit to
control the delivery of the stimulant 122 to the device 100. As noted
above, variations of the system include reservoirs that are fabricated
directly onto a body of the device 100. In such cases, the dispensing
unit/controller can be positioned on the device 100 body or can be
external to the device 100 such that a triggering signal is provided via
wired or wireless communication.

[0075] In addition to the above, variations of the devices described
herein or used in procedures described herein can position one or more
ports adjacent to specific taste receptors on the tongue. For example,
FIG. 3c illustrates a schematic view of a tongue to demonstrate the
various regions of taste. Typically, the port 106 is positioned adjacent
to the "sweet & salt" taste receptors that are positioned on an apex of
the tongue. However, ports can be additionally, or alternatively,
positioned to target "sour", "sweet", or even bitter taste receptors.

[0076] FIGS. 4A and 4B illustrate a condition as described above where an
individual is sleeping and the tongue 12 is in a retracted position
causing restriction of the airway 10 and inability of air as denoted by
arrow 30 to pass through the upper respiratory tract. In this variation,
the individual previously inserted a variation of an oral implant 100
within the mouth. Again, this variation of the oral implant 100 is nested
on one or more teeth 8 of the individual. FIG. 4A shows nesting of the
implant 100 on the top teeth while FIG. 4B shows nesting of the implant
100 on the bottom teeth. Again, additional variations allow for temporary
positioning anywhere that allows for the stimulant to induce a natural or
biological response.

[0077] The device 100 is coupled to a reservoir 120 containing a supply of
the stimulant 122. In one variation, the stimulant is delivered
intermittently. Alternatively, or in combination delivery of the
stimulant produces the biological response only when necessary. This
intermittent delivery reduces the probability of waking the individual.
The intermittent delivery also serves to minimize the chances of the
individual becoming desensitized to the stimulant. Delivery of the
stimulant can be intermittently paused based on any number of conditions.
For example, delivery or pausing delivery of the stimulant can be time
based, or can be based on sensor feedback as described below. Once
delivery of the stimulant occurs, as shown by arrows 32, the port 106
delivers the stimulant to a desired area within the mouth (e.g., a
surface of the tongue, underneath the tongue, etc.).

[0078] Delivery of the stimulant produces a natural response such as
salivation, forward movement of the tongue, repositioning of the tongue,
swallowing or a combination thereof.

[0079]FIG. 4c illustrates the effect of these natural response induced by
the stimulant. As shown, the tongue tends to reposition (as shown by
arrow 34). Any one of the natural responses or a combination thereof
causes opening of the previously constricted airway 10. This natural
response re-establishes airflow as shown by arrows 30 in FIG. 4c. As a
result, air can pass through the airway 10 to the lungs.

[0080] The biological response, in particular inducing saliva generation
in the mouth allows for pooling of saliva in the mouth, leading the
patient to swallow. The increased frequency of swallowing action
increases the muscle tone of the airway muscles. As the patient swallow,
the patient stops snoring and the upper airway obstruction clears.

[0081] The concepts and features described herein can be employed in any
number of devices. In certain variations, the devices include those
devices that fit within a mouth of the individual. For example, such oral
appliance can include mandibular advancement devices, a continuous
positive airway pressure device, a mouthguard, or a retainer.

[0082] FIGS. 5A and 5B illustrate one example of a mandibular advancement
device (MAD) 140 coupled to one or more sensors. Such sensors can include
a pressure sensor, an optical sensor, a sound sensor, a movement sensor,
an electro-magnetic sensor, or any sensor that can detect a condition
requiring delivery of the stimulant. For example, FIG. 5A shows a number
of sensors 142 positioned on an interior of the device 140. The sensors
can be coupled to a controller 146 (either via a wireless or a wired
connection) so that the sensor detects a pre-determined condition. When
the condition is triggered, the controller 146 and/or sensor can produce
a triggering signal to either start or stop delivery of the stimulant.
The sensor can be independent of the device 140 or can be positioned
outside of the body. Sensors for use with the devices and methods
described herein can be used to generate a signal based on a movement or
position of the tongue, measuring a degree of tongue movement with the
sensor and using the triggering signal to determine the amount of
stimulant based on the degree of movement. Alternatively, or in
combination, a triggering signal can be timed with an event such as
respiration, rate of respiration, a respiratory effect (e.g., wheezing or
coughing), respiratory flow, hypoxia, hypopnea, oxygen saturation, etc.

[0083] The position or force applied to a MAD can be used as a means to
trigger delivery of the chemoattractant stimulant. Mandibular advancement
devices are used to effectively treat snoring and OSA symptoms. The MAD
functions by maintaining the lower jaw in a prescribed position by
creating forward movement of the lower jaw with respect to the upper jaw.
This forward movement also creates space in the airway to relieve
symptoms. Conversely, in the absence of the lower jaw constraint relative
to the upper jaw, the potential airway space narrows with concomitant
return of symptoms. This lower jaw motion can correlate to the sleep
state of the patient and therefore can be used as a trigger to deliver
the stimulant during periods of sleep when snoring and OSA symptoms are
occurring. Accordingly, a mandibular advancement device can be configured
to sense the relative position or force of the lower component of the MAD
with respect to the upper component and the resultant change in position
or force used to trigger delivery of the stimulant. Alternatively or in
combination, the delivery of stimulant can be simply activated when a
threshold relative motion or force is reached. In another variation, the
amount of relative motion or force can be used to proportionately adjust
the dosing of the stimulant in the period that the motion or force is
measured.

[0084] The device can optionally include design features that have limited
intrusion into the mouth yet able to maximize the surface area of the
tongue in contact with the device. For example, a person resting in a
supine position will often have increase tongue obstruction due to
gravity. This is demonstrated by the example of a sleeping person who
improves or eliminates their snoring by rolling onto their side. An ideal
contact with the tongue in the supine position is along the bottom teeth.
In this position the tongue is resting on the floor of the mouth and
bottom teeth. Delivery of the stimulant onto the lower teeth can increase
the muscle tone of the tongue. This increased tone of the tongue is
intended to match to that of a person that does not suffer from snoring
or obstructive sleep apnea.

[0085] The device can have the form similar to that of a retainer that is
worn at night on the lower teeth. The retainer can be fitted with a port
or ports along the lingual side of the lower teeth. The port(s) can be
connected to a reservoir of stimulant discussed herein. Alternatively the
flavored compound can line the retainer along the aspect of the retainer
that is along the tongue. By placing the retainer and flavors along the
lower teeth, towards the back of the lower jaw, mandibular dental arch,
there is the additional advantage of stimulating the posterior portion of
the tongue. The glossopharyngeal nerve innervates that posterior (back)
one-third part of the tongue. Along with the Vagus nerve that senses
taste from the tongue, position and movement can be measured by using a
fiber optic sensor. For example, sensors commercially available from FISO
Technologies, Inc. Quebec, Canada suffice. The sensors have dimensions
and mechanical properties that enable the sensors to be positioned in the
mouth to obtain tongue position and tongue movement information without
disrupting the user in an awake or sleep state. The sensor can be
positioned in the mouth to obtain information relative to the location of
the sensor. More than one sensor can be positioned in the mouth to obtain
measurements either simultaneously or sequentially. For example a
pressure sensor can be incorporated into the mouthpiece as described in
the referenced provisional application. The amount of pressure exerted by
the tongue as it moves forward can be monitored on a subject during sleep
to obtain a baseline behavior. The tongue movement can be correlated to a
sleep state, thereby, obtaining tongue movement information that relates
to the status of the user. During treatment of snoring and OSA, tongue
pressure can be monitored as the regimen of stimulant is delivered. A
correlation between delivery of stimulant and tongue pressure can be
drawn to establish the effect of stimulant on tongue movement. In turn,
tongue movement can be correlated to a sleep state of the user, as
described above, to establish a correlation between tongue movement and
the effect of stimulant on the sleep state of the user. In another
example, a pressure sensor can be positioned in the space underneath the
tongue. The pressure measurement can be correlated to the position and
tone of the tongue and to the sleep state of the user. In another
example, two or more position sensors can be placed in the mouth and
tongue movement can be monitored with respect to the sensors.

[0086] FIGS. 6A to 6E illustrate additional variations of oral devices 100
for use as described herein. FIGS. 6A and 6B illustrate an oral device
100 similar to that shown above having a dispensing port 106 that can be
used to deliver a stimulant to the oral cavity, mouth and/or tongue. The
port 106 is coupled to a supply of the stimulus via a tube 108 that forms
a part of a fluid path between the supply or reservoir of the stimulus
and the port 106. In this variation, the tube 108 includes a fitting to
allow for coupling to an external reservoir. As described in further
detail below, a valve (not shown in FIG. 6A) can be located between the
port 106 and the reservoir. Alternatively, the valve can be positioned at
the port 106. As noted above, some variations of the device do not
include a valve. Instead, the device uses a pressure differential to
drive the stimulant through the port.

[0087] FIGS. 6C and 6D illustrate another variation of an oral device 100
where the dispensing port 106 includes a roller 128. The roller ball can
be replaced with a sponge or other similar type structure. The
stimulation elements (roller, sponge, etc.) can be smooth or incorporate
a texture and have a rigid or soft consistency that can be used to
deliver a stimulant to the oral cavity, mouth and/or tongue. The use of
the stimulation elements can optionally eliminate the need for a valve
for metering the stimulant.

[0088] FIG. 6E illustrates another variation of an oral device 150 for use
as described herein. In this example, the oral device 150 is configured
to function as an upper jaw retainer, with a receptacle 152 for the
teeth, and with a reservoir 154 that contains a capsule in the upper hard
palate region 156. The stimulant can include a typical gelatin capsule
that dissolves in water or saliva in about 15 to 30 minutes. This time
range is typical for people to fall asleep. Once the capsule dissolves
the taste compound inside the capsule starts to leach out of the capsule
into the patient mouth triggering access salivation. In order to prevent
the citrus compound from releasing all at once, the citrus compound can
be in the form of a "hard candy" like form. Alternatively, the reservoir
154 can be replaced with a supply line that couples the device 150 to an
external supply of the stimulant.

[0089] In another embodiment of this invention the taste compound could be
in a compartment in the mouthpiece or retainer and having a valve. The
valve can be controlled by an electronic switch. The sequence of the
release of the taste compound can be programmed to be once every few
seconds to few minutes. In another embodiment of this invention the taste
compound is in a compartment in the mouthpiece or a retainer and has an
electronically controlled valve. In addition the electronic circuit for
the valve control is designed to receive a trigger signal for the release
of taste compound in pre-determined dosage. The signal could be triggered
by monitoring a user's vital signal to assure that user is asleep prior
to start releasing taste compound.

[0090] FIG. 7A illustrates another variation of a dispensing device 170 in
which the device 170 simply comprises a stimulant tube 172 and a scent
tube 174 each coupled to a reservoir or controller 176 that houses the
respective stimulant and/or scent. Alternate variations contemplate the
use of an aromatic stimulant such that scent is triggered by the mere
deployment of the stimulant. As shown in FIG. 7A, the tubes 172 and 174
are merely affixed to the patient to intermittently deploy the stimulant.
In an alternative variation, the tubes can be combined into a single
tube. Furthermore, the tubes can optionally be fitted with the sensors
discussed herein.

[0091]FIG. 7B shows a Constant Positive Airway Pressure (CPAP) device 180
combined with the teachings disclosed herein. As shown, the CPAP device
180 can include a separate supply 182 to couple the CPAP device 180 to a
source 184 of a stimulant 186. Alternatively, the CPAP device can be used
with a self contained device as disclosed above.

[0092] The stimulant described above can take the form of a liquid of low
or high viscosity, a solid, a semisolid or paste, a gas or a combination
thereof. The properties of the stimulus are such that delivery within the
mouth causes a biological or natural reaction. This reaction can include
generation of saliva to cause swallowing but in an amount that does not
awaken the user from a sleep state. Alternatively or in combination, the
stimulant can cause movement of the tongue or repositioning of the tongue
in a forward position against the teeth.

[0093]FIG. 7c illustrates yet another variation of a dispensing device
170 in which the device 170 comprises a stimulant tube 172 coupled to a
solution supply 173. A stimulant supply 186 can feed into the solution
supply 173 along with a second substance 187. One variation contemplates
the second substance 187 to dilute the effects of the stimulant to allow
for continuous dispensing of the solution over a period of time during
the night or periodically.

[0094] The stimulant can comprise any number of tastes including, but not
limited to sweet, sour, bitter or salty.

[0095] Examples of liquid stimuli are solutions of Xylitol, saline and
citrus. Smell stimuli include odors and fragrances that stimulate
salivation and swallowing during sleep, such as banana, strawberry,
orange, other fruits, vanilla, or mint. Preferably the stimuli can be
delivered to the user over normal periods of sleep and as a long term
therapy for snoring or sleep apnea, without causing untoward effects to
the anatomy and physiology, such as degradation of the teeth or gastric
disturbances. In the cases of taste and smell stimuli, the stimulation
appliance incorporates a reservoir that allows for delivery of the
stimulus over the sleep period.

[0096] Alternatively, in another embodiment, the compound that increases
salivation could be other fruit flavors or other food flavors of the
particular user's choice. The mouthpiece or retainer is either designed
for repeated use or disposable. Once the user wakes up in the morning,
he/she will remove the device out of the mouth, rinse it and allow it to
dry. Next night prior to sleeping, the patient would insert a capsule
containing taste compound in the device or reload the taste compound
reservoir, place it in the mouth and fall asleep. In the case of a
disposable mouthpiece, optionally the capsule or reservoir could be
packaged preloaded with the taste compound or allow for placement of a
capsule or filling of a reservoir, similarly to a reusable device. In
another embodiment the reservoir comprises a primary reservoir, a
secondary reservoir and a passive valve on the secondary reservoir that
opens at a prescribed pressure. The primary reservoir which contains the
taste compound fills the secondary reservoir at a uniform flow rate
through an orifice between the reservoirs. The driving force for flow
between the primary and secondary reservoir is enabled by gravity or,
optionally, by a plunger driven by a spring. The secondary reservoir
fills until it reaches a volume that exerts the cracking pressure of the
passive valve, allowing delivery of an aliquot of the taste compound.

Example 1

[0097] As discussed above, abnormal head and neck anatomy and decreased
pharyngeal dilator muscle tone are two primary contributors to OSA. Both
conditions affect the tongue and result in the tongue's having a central
role in OSA. One variation of a device using a stimulant (e.g., a
flavored substances) to engage the tongue and alleviate tongue-related
obstruction can include the use of one or more pressure sensors within
the existing intraoral device. For example, FIG. 2A illustrates sensors
116 that will detect the presence or absence of the tongue in a desirable
position within the mouth. FIG. 8A illustrates one example of a
fiberoptic pressure sensor (supplied by FISO Technologies Inc., Quebec,
QC, Canada).

[0098] In this example, the outer diameter of the sensor was 260±20
μm, and the outer diameter of the fiberoptic cable connecting to it
(extending from the subject's mouth when deployed) was 1 mm. In some
variations it is important that the sensors not interfere with tongue
movement. Also, the pressure sensor (in this case the fiberoptic cable)
should be well-tolerated due to its small size. In the variation used,
two sensors 190 (FOP-M260 sensors) are placed within the intraoral device
(as shown in FIG. 2A) on the lingual aspect of the dentition 116 to
enable direct tongue contact. The locations chosen are anteriorly in the
midline and more-laterally, between the canine adjacent to the first
premolar. However, alternate placement of the sensor is well within the
scope of this disclosure. In the present example, the sensors could be
secured in position with the use of medical-grade adhesive against the
intraoral device, identically as for the stimulant supply tubing 108.

[0099] In cases where an optical sensor is used, the sensor relies on
Fabry-Perot whitelight interferometry to use a light source (bright
incoherent light) that is split 50/50 within a 2×2 coupler. The
light passes through the optical connector and optical fiber to reach the
sensor, which is a Fabry-Perot interferometer (see FIG. 5). Within the
sensor, the light is reflected, but a large number of parallel beams
escape the optical fiber core. These are redirected back into the optical
fiber core, creating a light interference pattern that is associated with
the distance between the semi-reflective mirrors in the sensor. Changes
in pressure at the sensor tip alter the length of the Fabry-Perot cavity
in the sensor and thereby change the interference pattern. The light from
the sensor is reflected back through the optical fiber to the coupler.
The coupler then splits the light, with half of this light directed back
to an optical box, where it is spread over a Fizeau wedge that
reconstructs the interference pattern and records it with a
charge-coupled device.

[0100] Use of the FISO Technologies FPI-HR system in combination with the
oral implant device described above allows for acquisition of pressures
using the FOPM260 sensor at up to 15 kHz over a range of -300 to +300 mm
Hg and accuracy within 2 mm Hg. Although two sensors were used and enable
a more-thorough assessment of tongue neuromuscular activation than is
possible with one sensor. Any number of sensors is contemplated within
the scope of this disclosure.

[0101] FIGS. 8B and 8C demonstrate the results of a custom fitted oral
appliance (similar to that shown in FIG. 2A). In the experiment a patient
received a 40% xylitol solution infused into the anterior oral cavity for
5 minutes at a constant rate of 0.1 ml/min. The infusion was initiated
every 10 minutes, producing an alternating pattern of 5 minutes on, 5
minutes off throughout the night. FIG. 8B presents the apnea-hypopnea
index (AHI) results for individuals with mild to moderate OSA, while FIG.
8B presents the apneahypopnea index (AHI) results for individuals with
severe OSA. Overall, there was a decrease in the apnea-hypopnea index
(AHI) from 37.5 to 17.1 events/hour, with the decrease from 16.0 to 7.1
in mild to moderate OSA and 69.7 to 32.3 in the severe OSA group. The
changes in the mild to moderate OSA subgroup, including the decreases in
AHI of >50% in all subjects and the low levels of residual AHI, have
led to the eligibility criterion of mild to moderate OSA in the proposed
clinical trial. In addition to the reduction in AHI, there was a
corresponding decrease in the arousal index and no change in sleep
architecture (normal percentage of time in REM sleep).

Example 2

[0102] 1. Introduction:

[0103] The tongue plays an important role in snoring and obstructive sleep
apnea, contributing to turbulent airflow and upper airway obstruction
during sleep. An intraoral device is used in this experimental example to
deliver flavored substances in the anterior oral cavity, with the goal of
induced tongue chemoactivation and anterior tongue movement towards the
flavored substances. The effect of this chemoactivation is to open the
airway by overcoming the natural decrease in muscle tone during sleep
that leads to posterior tongue prolapse. In this study, tongue sensors
were incorporated into the intraoral device, placed immediately posterior
to the maxillary (upper) central dentition. The objective of this study
was to examine tongue chemoactivation and anterior tongue movement
associated with the administration of flavored substances in the anterior
oral cavity.

[0104] According to one aspect illustrated by this experimental study
example, a tongue position sensor ("TSE") assembly and method is
configured to detect tongue repositioning activity to the sensor
position. Moving the tongue anteriorly into such a position, in
particular toward the front teeth, repositions the tongue out of the
posterior pharynx.

[0105] This TSE approach monitors the presence, and absence, of this
protective tongue repositioning activity against pharynx obstruction. The
specific TSE embodiment constructed under this experimental example is
not necessarily configured for the additional directed purpose to also
measure all tongue positioning activities--and some of which are present
in the normal individual to prevent obstructive events. Pathology will
generally occur via the tongue receding to the posterior pharynx and
causing obstruction. It is also considered highly beneficial to detect
the presence any one of multiple protective tongue activities, as
indicating a likelihood that the tongue is non-obstructively positioned
relative to the posterior pharynx. In the setting of a therapy intended
to achieve this result, such detection also confirms the functional
success of the therapy.

[0106] Devices and related methods that are configured to reposition the
tongue out of the posterior pharynx have been proposed, and constructed,
tested, and demonstrated that such tongue repositioning may resolve or at
least improve these obstructive events and other related disorders.
Certain such approaches are configured to stimulate tongue movement for
such repositioning, i.e. as tongue repositioning stimulators ("TST").
Such a TST may be configured and operated by a number of mechanisms and
methodologies. Certain exemplary embodiments include, without limitation:
(1) the TST may be configured and operated to apply a force to the tongue
to directly move it into the desired anterior position; or (2) the TST
may be configured and operated to apply a stimulation which invokes a
biological response in the subject which moves the tongue into the
desired position; or (3) a combination of (1) and (2). Certain further
embodiments of (2) above include, without limitation, a stimulation media
which is delivered via an appropriately configured TST assembly and
method in a manner to stimulate a response to cause the tongue
positioning. This stimulation media may comprise, according to further
embodiments, and without limitation: (a) a fluid, and which may typically
be a liquid, though may also be a gas; (b) a semisolid, paste, or gel;
(c) a solid; (d) a flavor, taste, or smell invoking the responsive tongue
movement; or (e) a combination of any of the preceding, i.e. a fluid
flavor stimulus, such as for example a liquid flavor or taste
stimulus--as is used in the present experimental study example.

[0107] Another aspect of the present disclosure provides a TST may be
configured for passive delivery of the stimulus, such as for example
simple passive dissolving of a stimulus material or diffusion of a fluid
into the mouth.

[0108] However, according to another aspect of this disclosure exemplified
by the present experimental study, a TST may comprise controlled delivery
of the stimulus, i.e. as a controlled TST or "cTST." According to one
beneficial mode of this aspect, the cTST comprises a controller which
controls the stimulus delivery. In certain beneficial embodiments, this
comprises controlled delivery of a stimulus media, which may be in
further embodiments, for example but without limitation, at least one of
a fluid and a flavor stimulus. A cTST comprising a controller to control
delivery of a fluid flavor stimulus is provided and used under the
current experimental study.

[0109] The controller of a cTST may control stimulus delivery according to
various different desired delivery profiles, e.g. amounts, rates, or
"dosage" regimen of the stimulus therapy over time. According to one
embodiment, this comprises a relatively fixed profile for constant
delivery or dosing regimen of the stimulus therapy over time (such as for
example during sleep). However, according to another embodiment, this
comprises controlling the delivery profile and dosing regimen to change
over time, e.g. between different conditions (i.e. amount and/or rate of
stimulus delivery). Such changing profile may comprise, for example, a
continuous rate of change, or discontinuous rate of change, or a
combination thereof in different time intervals, over a therapy dosage
period (e.g. during sleep). This change can be between on and off
conditions--either in absolute terms, or in functional context with
respect to being above or below, respectively, a threshold for achieving
the intended results of stimulation. It is thus appreciated that this
controlled delivery may be modulated to change between levels of applied
stimulus (which may be according to a pattern, such as a cycle; or may be
another form of changing profile).

[0110] The controller of a cTST system and method may comprise a
relatively simple control mechanism, or may be more complex. According to
one example, it may comprise a pump for delivering a fluid stimulus
according to either fixed or adjustable delivery rates, change(s) in
rate, and/or other settings which may be either manual or automated, or a
combination thereof. The controller may also comprise a computer software
program embedded in a non-transitory computer readable medium and
configured to be run by a processor, and/or a processor configured to run
and process an embedded computer software program in a non-transitory
computer readable medium.

[0111] The current experimental example involves a particularly beneficial
cTST embodiment which comprises a controller, liquid stimulus source, and
oral delivery assembly--all assembled in an overall system for controlled
pump delivery of the liquid flavor stimulus at an anterior location
within the mouth, in particular behind the front teeth. The flavor
stimulus applied in the proper position, in particular posteriorly
adjacent to the front teeth, stimulates movement of the tongue forward
into the proper anatomical position and out of the posterior pharynx
(i.e. protective tongue repositioning activity). In addition to this type
of protective repositioning, there may also be additional protective
responsive mechanisms, such as that muscle tone is improved sufficient to
remove the tongue out of the posterior pharynx such that it is no longer
obstructing breathing.

[0112] According to another aspect exemplified by the embodiment of this
experimental example, a TST is provided in combination with a tongue
position sensor (or "TST-TSE") system. According to one mode of this
aspect, the TSE is used to assess the performance of the TST to stimulate
the tongue into the anterior protective repositioning activity. According
to another mode, a cTST is combined with the TSE to form a "cTST-TSE"
combination system. Further to this mode, the sensed tongue position
information provided by the TSE is used as a real-time diagnostic basis
and input into the cTST, and at least in part by which the configuration
and operation of the controller of the cTST is based. In one embodiment,
in response to the TSE sensing an absence of (or reduction or movement
away from) the anterior protective position, the cTST is configured and
operated to control the stimulus delivery to apply the stimulus in a
manner that causes the tongue to move into the anterior protective
position. In another embodiment, in response to the TSE sensing the
tongue is in the anterior protective position, the cTST is configured and
operated to control the stimulus delivery to stop or reduce the
application of the stimulus. This may provide a benefit, for example, to
prevent overstimulation and potential wakening of the subject, or prevent
habituation or desensitization of the tongue movement response to the
applied stimulus.

[0113] 2. Purpose:

[0114] The current study was designed and conducted as a 14 day trial of a
single control subject without a history of obstructive sleep apnea. The
test subject was subjected to consecutive nightly exposure to a liquid
stimulus, xylitol, administered in the anterior chamber of the mouth (or
anterior oral cavity). This was conducted via a new and useful cTST
delivery assembly and method constructed for stimulant delivery via an
oral appliance according to a particularly beneficial embodiment of this
disclosure. A TSE was also included, also incorporating the oral
appliance, in an overall cTST-TSE system. The hypothesis entering the
experiment was that the TSE will be able to demonstrate the anterior
protective tongue repositioning activity in response to this applied
xylitol exposure via the cTST, thus showing that in response to the novel
cTST therapy:

(a) the subject's tongue moves forward into the anterior protective
position, and will trigger the sensor of the TSE; and (b) the anterior
protective tongue repositioning activity is repeatable night after night
and does not habituate or disappear over the two week period.

[0115] During the 14 night trial, certain parameters were varied to
compare effects, via changes in pressure at the sensor of the TSE, of
various rates and intervals of xylitol exposure via the cTST, including
examining for differences in acute responses for multiple infusion rates
and dosing intervals as well as for habituation over the 14 day period.

[0119] A custom mouthpiece was configured as a dental tray made by
thermoforming a plastic retainer to a mold of the patient's teeth. The
custom configuration constructed and used is palatal arch-less, and
secured by form fitting to the teeth. This shares certain similarities to
such dental retainer trays made and sold under the name "Invisalign®"
or otherwise for braces or certain teeth whitening trays. However, the
current dental tray retainer also comprises certain distinct differences
which are both structurally and functionally unique--and exemplify
various inventive aspects of the present disclosure concordant with the
unique functional purposes intended.

[0120] The dental retainer is vacuum formed with an Essix® Vacuum

[0121] Thermoforming Machine, model #85000 sold by "Dentslpy®." While
various materials may be suitable and used for this purpose, the material
chosen for this particular experiment is plastic, and more specifically a
Dentsply® plastic: "PET Essix A+." The plastic tray was constructed
for this particular experiment with a wall thickness of about 0.02
inches.

[0122] As two particularly unique features of the present embodiments of
this example, two tubes were also secured to the tray, in particular by
UV bonding each of two IV tubes to the tray for purpose of this specific
experiment (though other bonding, securement, or integration of the
features may be sufficient). These tubes were secured in a configuration
to create two ports, respectively, on the posterior lingual side of the
anterior two front teeth--and which were generally adjacent or "side by
side" (though exact side by side adjacency is not considered absolutely
necessary, and other relative locations may be suitable). The tubes were
also configured to extend anteriorly away from the tray, teeth, and mouth
and externally of the patient. This construction provides the unique
custom result of a delivery tube and respective delivery port for
stimulus delivery to the posterior lingual side of the anterior teeth,
and sensor tube and respective sensor port at a similar, generally
adjacent, location. In the physical embodiment constructed for this
experiment, these tubes terminated in luer lock ports. One port was
connected to an infusion pump, with a 30 BD syringe filled with the 40%
xylitol solution.

[0123] b. Liquid Flavor Stimulus

[0124] Xylitol sugar (sweetener frequently used, such as for example in
Trident® gum) was mixed with tap water in 40% concentration to provide
the liquid flavor stimulus. This was retained and dispensed during the
experiment using a standard, commercially available 30 ml "BD" Syringe.
Delivery was accomplished via the standard small bore IV tubing noted
above as secured to the TST-TSE dental retainer.

[0125] c. Stimulus Delivery Controller

[0126] An infusion pump (Baxter® AS40® Auto Syringe Infusion
Pump®) was also provided to control the delivery via the syringe, via
delivery profile parameters that were configured to a variety of settings
for purpose of the test agenda and hypotheses.

[0127] d. Pressure Sensor

[0128] Pressures were collected using a commercially available
FOP-F125® pressure sensor. This sensor was located adjacent to the
inlet port for infusion of the xylitol solution, directly behind the
maxillary (upper) central dentition. The sensor tip was positioned within
an auto-inflating, cotton fiber-filled polyurethane bubble that was
designed as part of a closed system with the sensor. The pressure sensor
was also coupled to the pressure tubing secured to the TST-TSE dental
retainer. The sensor was also connected to a signal processor and the
signal processor was connected to a PC with analytic software. More
specifically, it was connected to a FPI-HR Module® signal conditioner
(manufactured by FISO® Inc.). Data collected was then recorded to a
standard PC, using Evolution® software also provided by FISO® Inc.

[0129] 4. Methods

[0130] The test subject was fitted with the custom TST-TSE retainer. One
proximal port was connected to the infusion pump, per the 30 BD Syringe
filled with 40% Xylitol solution. Xylitol infusion rate was set at
various parameters, as described in further detail below.

[0131] A second proximal port was connected to IV pressure tubing, leading
to a sealed chamber containing the sensor. The sensor was connected to a
signal processor and the signal processor was connected to a PC with
analytic software, as described above.

[0132]FIG. 9 shows an embodiment of the cTST-TSE system 200 described
above, with certain components shown schematically for simplicity. More
specifically, FIG. 9 shows (though not readily visible as it is clear) a
cTST-TSE retainer 202 on a white model of teeth 201, with tubes 204, 206
extending from the cTST-TSE retainer 202 and terminating in couplers such
as shown at luer lock 208 for tube 206. These tubes are fluidly coupled
via passageways formed in the retainer 202 to a dispensing port and
sensor, respectively, at adjacent delivery and sensor locations,
respectively, on the central anterior aspect of the oral cavity
posteriorly adjacent to the middle two front incisor teeth (not revealed
in the detail shown). Tube 204 comprises a delivery tube and is also
fluidly coupled to a controlled stimulus delivery assembly 210 located
externally of the mouth and comprising a source of stimulant 212 and a
controller 214. Tube 206 comprises a sensor tube and is also fluidly
coupled to a pressure sensor processing assembly 216 via luer lock
coupler 208.

[0133] Stimulant from the source 212 is delivered via delivery tube 204 to
the dispensing port at the delivery location. In response, the tongue is
stimulated to be repositioned to an anterior protective position against
the front teeth and thus with applied pressure against the sensor at the
sensor location. This is conveyed via sensor tube 206 to the sensor
processor 218. In a cTST system, the sensed pressure is converted to a
signal with a value that is communicated to the controller 214 in a
feedback coupling 216, e.g., electrical communication between the two
appliances. While it is considered a beneficial embodiment (though not
necessary) of the present disclosure to control the stimulus delivery via
the sensed tongue position, this coupled feedback loop between was not
incorporated into the current experimental study design. In the current
experimental design, the sensed pressure is processed into data which is
recorded for analysis, as shown at block 220 schematically in FIG. 9.
Screen shots and data files were collected for comparative analysis.
Controlled stimulant delivery was instead managed by pre-determined
parameter inputs to the controller under a controlled experimental design
with controlled ranges of delivery variables.

[0139] (b) from 1,000 to 3,650 seconds, the device is in place but OFF.
The recorded pressures during this period reveal no apparent anterior
protective tongue repositioning against the sensor during the OFF mode;
and

[0140] (c) starting at 3,750 seconds, the controlled pump device assembly
is set to continuous on. Recorded pressure results show an appreciable
amount of anterior protective tongue repositioning activity during this
period.

[0141]FIG. 11 also shows a graph of results according to sensed anterior
tongue pressure vs. time (example, OFF only). The device is in place and
worn by the subject, but set to OFF. The results demonstrate there is
almost no anterior protective tongue repositioning activity when the
controlled stimulus delivery device is turned off:

[0143] (b) the recorded pressure data over the rest of the recording
period reveals virtually no anterior protective tongue repositioning
activity, though the tongue is not believed to have been obstructive to
the pharynx (perhaps due to good tone or other protective position), as
evidenced by lack of suspected obstructive events or related sleep
disorder.

[0145]FIG. 12 shows a graph of frequency of sensed anterior protective
tongue positioning events (per second) vs. time (consecutive nights over
14 day period), according to this test protocol. More specifically, FIG.
12 shows graphical results using the same rates and intervals on four
separate nights throughout the 14 day trial demonstrating that the tongue
activity is generally repeatable (obviously within a certain range of
variability) night after night and does not reveal a trend that there is
habituation to the stimulus or disappearance of the biologic
repositioning response over the two week test period.

[0146]FIG. 13 shows a graph of same results featured in FIG. 12, per
frequency of sensed anterior tongue positioning events (per second) vs.
time (consecutive nights over the 14 day period, in split-night view).
However, FIG. 13 shows a closer look at the same nights in same test
subject, comparing the first half of the night to the second half (i.e.
"split night" view or analysis). While again certain range of variability
is shown, out to night 14 similar activity is observed as was observed at
night 4, and without significantly apparent difference between first and
second halves of the night on that 14th night following continual
treatment over the 2 week period.

[0148]FIG. 14 shows a bar graph of results according to frequency of
sensed anterior protective tongue repositioning events (per second) vs.
time (consecutive nights over 14 day period). More specifically, the FIG.
14 bar graph shows results of using a shorter interval than the pilot
trial protocol with various rates. As shown over this test period, the
sensed frequency of anterior protective tongue repositioning activity
appears to reduce in direct relationship with reducing stimulant delivery
rate across the matrix from 100 uL/min on night 5 to 25 uL/min by night
13. This again suggests confirmation that the stimulant delivery appears
to be playing an active role in the desired tongue repositioning
activity.

[0149]FIG. 15 also shows a bar graph of results per frequency of sensed
anterior protective tongue repositioning activity events (per second) vs.
time (consecutive nights over 14 day period). However, while FIG. 15
provides a closer look at the same nights in same subject as FIG. 14,
this graph of FIG. 15 compares the first half of the night to the second
half (when available) in split night analysis.

[0151]FIG. 16 also shows a bar graph of frequency of sensed anterior
protective tongue repositioning activity events (per second) vs. time
(consecutive nights over 14 day period). However, this is a graph of
results during continuous flow, with no pauses in delivery of xylitol,
but comparing two different stimulant delivery rates. An obvious
reduction is apparent in sensed events in direct relationship to the
reduction from the 150 uL/min rate on night 1 (about 9.5 events), and the
33 uL/min rate on night 12 (<4 events)--in fact the >50% reduction
in delivery rate resulted in >50% reduction in the desired tongue
repositioning events.

[0152] 6. Additional Analysis/Discussion

[0153] FIG. 17 shows a graph of sensed tongue movement to the protective
anterior position as a function of varying stimulant delivery rates. The
results show that tongue movement is maintained at even lower rates. It
is noted that with no flavor there appears to be a considerable drop-off
in response. It is also noted in this data that certain points reflect
continuous on, whereas others represent cycled on/off conditions (as
reflected in the legend).

[0154]FIG. 18 also shows 14 days of consecutive treatment at various
rates and protocols.

[0155] The current Example 2 reflects data from a 14 day trial of a single
control subject, without a history of obstructive sleep apnea. A
consecutive nightly exposure to xylitol was administered in the anterior
oral cavity via the novel cTST-TSE system described.

[0156] The experimental data demonstrates that the tongue moves forward
and is drawn to the anterior oral cavity against the front teeth with the
novel anterior protective tongue repositioning stimulation treatment
used. The affect is not appreciably present with the device in place and
turned off. The presence of the oral appliance alone, not turned on, is
not sufficient to cause the movement of the tongue. Additionally, the
study also reveals that this cannot be optimally achieved just by using
plain water without a flavor, since the presence of flavor appears to
greatly enhance the tongue movement--as reflected in this data. This
clearly demonstrates the mechanism of action, where the tongue is
stimulated to come forward in the presence of flavor stimulus when
administered according to the unique systems and methods used in this
experiment. This is expected to provide protective benefit during sleep,
since it is known that bringing the tongue forward from a posterior
position to the anterior oral cavity as in this experiment clears the
posterior pharynx and reduces symptoms of obstructive sleep apnea.

[0157] In addition, there was no appreciable habituation observed after
two weeks of this unique therapy. There were different rates used over
the 14 day study, but comparing the four nights of standard rates
"protocol" of treatment (i.e. on for 5 min then off for 5 min) no
relevant decrease in tongue activity is observed. In fact, the second two
nights of this treatment resulted in a greater frequency of tongue
movement than the first two protocol nights. This suggests support for a
hypothesis that there is actually a conditioning response that takes
place, and that successive treatments grow stronger in their stimulation
impact and results.

[0158] The observations in this study also reveal that the variability of
response using different rates and hourly volumes appears to be within
the night to night variability of identical treatments. This suggests
that the frequency of tongue movement is not likely to be solely
dependent on the volume of delivery. Volumes can be reduced such that the
frequency of stimulation, the anterior movement of the tongue is
consistent.

[0159] As would be readily appreciated by one of ordinary skill, while
certain specific values and other numbers are recited herein this
disclosure, and are considered to provide particularly beneficial
examples, unless otherwise stated such values are not intended to
necessary limit the broader aspects of the disclosure which they
exemplify. Unless stated otherwise, such exemplary values are not
necessarily considered exact or absolute--and the exemplary values should
be considered in "about" terms. Slight variances may be made to
specifically stated values or ranges without departing from the broad
aspects exemplified. For example, most dimensions or performance
measures, whether stated in the singular, ratio, or range for example,
will typically be subject to certain tolerances of the materials,
structural designs, operating environment, and methods embodied in the
featured numbers. Moreover, variations may also be deliberately made from
such specific values disclosed, but while still accomplishing similar or
equivalent objectives and results, and still falling within the broader
aspects of the disclosure. For example, while remaining subject to and
without limiting the preceding aspects of this paragraph above, a
tolerance of plus or minus about 10 to about 20 percent of such specified
values will typically still be considered equivalent and falling within
the intended scope of the specific values herein described.

[0160] As would also be apparent to one of ordinary skill, such "values"
noted immediately above relate to quantitative or "numeric" values, and
also qualitative values. For example, certain exemplary embodiments
described hereunder recite an "intermittent" stimulus delivery, and which
in certain further embodiments is described to be between "on" and "off"
conditions or states of stimulus delivery. It is readily appreciated by
one of ordinary skill that such conditions or states should be considered
contextual to the related purpose and intended functional results of the
respective states. For example, an "on" condition or state of stimulus
delivery may be achieved when the stimulus is delivered at or above a
certain threshold intended to achieve a functional stimulated result;
whereas conversely and "off" condition or state of stimulus delivery may
be achieved by a stimulus delivery profile or dosage regimen below that
threshold--i.e. functionally equivalent, contextual to the intended
result of stimulation, to a complete cessation of any stimulus delivery.
Moreover, while an "intermittent" change may be accomplished in discrete
intervals that may not be continuous, a continuous change in stimulus
delivery amount or rate may be equivalent to an interval change when the
change is between such "on" and "off" conditions relative to being above
or below a stimulus threshold, respectively.

[0161] The present detailed embodiments have been variously described by
reference to delivering stimulants or stimulus, and in more particular
applications specifically for delivering stimulants to the mouth for
stimulating a tongue, and in further detail for stimulating tongue
repositioning, and still more specifically to Type 1 or anterior position
within the mouth. However, other therapies may also be delivered
according to these systems and methods and still fall within the broad
intended scope of the various aspects contemplated hereunder.

[0162] For example, various different therapeutic agents may be delivered
according to the systems and methods herein described. Such agents may be
for example materials or molecular agents, which may be in various
different preparations for delivery, such as fluid (e.g. liquid or gas),
solid, semi-solid, gel, paste, suspension, powder, etc. Or, the
therapeutic agent may be in another form such as an electrical current
(e.g. RF current for example), thermo-energy (e.g. either heating or
cryo/cooling), optical energy (which may provoke an optical response in
tissue or provide another form of thermal heating), etc. For one more
detailed example for purpose of further illustration and understanding, a
low current/voltage RF signal may be delivered similarly in context of
the oral delivery systems and methods as described herein with respect to
delivering a fluid flavor stimulant (e.g. according to the "Examples").
This may be either in the alternative or addition to such fluid stimulant
delivery. For example, delivering such electrical current to a similarly
positioned anterior location in the mouth, such as described above for
delivery port of the xylitol delivery of Example 2 (e.g. lingual side of
front incisor teeth), may also stimulate a tongue repositioning response
into the anterior position of the mouth as desired. In another more
detailed illustrative example, such current may be delivered via a
current source either coupled directly to the oral device or from outside
the mouth via a delivery assembly (e.g. electrically via electrical leads
similar to fluid coupling via delivery tubes described above). In a
further example, this current may also be exposed at an electrode which
is located at similar position as the fluid delivery port of the Example
2. In such example, the electrode may be bi-polar with the two electrodes
on the oral device itself, or may be monopolar and work via a ground
patch placed elsewhere on the patient (as in other RF current medical
device assemblies previously disclosed).

[0163] Also in the alternative or combination with one or more of the
above examples, a thermal heating or cooling element may also be provided
at such a location on the oral device in similar anterior position within
the mouth--and which may also provide such tongue stimulus for
repositioning.

[0164] Other variations or modifications to the detailed embodiments above
can also be made, and remain within the broad aspects intended to be
captured by this disclosure. For example, many different specific sensors
and related structural arrangements, for sensing various different
parameters, can be incorporated into the sensor embodiments herein shown
and described, as well as other embodiments as would be apparent to one
of ordinary skill based upon a review of this disclosure.

[0165] For further example, optical sensors may be employed, with various
alternative assemblies coupling them to mouthpieces. According to one
such example for illustration, a light source is coupled to an
illumination port on the oral device and configured to transmit an
illumination light signal from the illumination port into the mouth. The
sensor according to this arrangement may comprise an optical sensor
coupled to the oral device at the sensor location. Further to this
arrangement, the sensor location is positioned relative to the
illumination port such that the optical sensor is configured to sense a
reflected light signal that is reflected in the mouth from the
illumination light signal transmitted into the mouth from the
illumination port.

[0166] According to an additional embodiment, an optical fiber is provided
with a first end portion with a first end optically coupled to the oral
device at the sensor location and also to the mouth in the implant
configuration, and a second end portion coupled to the optical sensor
located outside the mouth when the oral device is in the implant
configuration. Further to this example, the reflected light signal is
optically coupled from the sensor location in the mouth to the optical
sensor outside of the mouth via the optical fiber.

[0167] In another particular example for further illustration, an optical
fiber is provided with a first end portion with a first end optically
coupled to the oral device at the illumination port and also to the mouth
in the implant configuration, and a second end portion coupled to the
light source located outside the mouth when the oral device is in the
implant configuration. Further to this example, the illumination light
signal is optically coupled from the light source outside of the mouth to
the illumination port and into the mouth via the optical fiber.

[0168] According to another example, an optical fiber couples the
illumination port on the oral device in the mouth, at a first end of a
first end portion of the optical fiber, to the light source located
outside the mouth, at a second end of a second end portion of the optical
fiber; whereas an optical fiber also similarly couples the sensor
location on the oral device in the mouth to an optical sensor outside of
the mouth.

[0169] Still further variations are contemplated according to this
example. In one such further variation, the illumination port and the
sensor location are coupled to the oral device at first and second
separate but adjacent locations; and the first and second end portions of
each of the fiber optic delivery members are separate, distinct fiber
optic delivery members. Further to this variation, the first end portions
of each of the first and second fiber optic delivery members may also be,
at least in part, bundled adjacently together. According to another
variation, the first end portions of each of the first and second fiber
optic delivery members comprise the same common fiber optic delivery
member. According to another variation, the second end portions of each
of the first and second fiber optic delivery members comprise the same
common fiber optic delivery member; and the light source and optical
sensor are each coupled to the common second end (typically with a
splitter, separator, or other mechanism known in the art for measuring
transmitted and reflected light via a common fiber optic. In still
another further variation, where a common optical fiber is used at the
first end coupling to the device for transmitting and receiving reflected
light at the optical interface in the body, the second end portion is
bifurcated to comprise first and second optical couplers. The first
optical coupler is configured to be coupled to the light source, and the
second optical coupler is configured to be coupled to the light sensor.
Further to this variation, light transmitted from the light source via
the first optical coupler and light received by the light sensor via the
second optical coupler are transmitted via the common first end portion
of the optical delivery member.

[0170] Furthermore, other therapies may be also be provided for delivery
and use according to the structural system and method aspects, and the
exemplary embodiments of this disclosure. This also may be either in
addition to or in the alternative to the specific therapies also herein
described. For example, this may include therapies other than tongue
stimulation or repositioning, other stimulant delivery and stimulus
therapies related thereto, or other therapies than stimulation or
delivering, or other therapies than those which may be related to the
tongue. For example, other therapeutic agents may be employed for other
medical or dental purposes, such as for example pharmaceutical agents
(e.g. drugs), as the present disclosure provides for a beneficial new
approach for oral drug delivery. Accordingly, a wide range of
applications may be satisfied for many different target objectives
suitable for such oral agent delivery and consumption. This may include
something as simple as delivering antiseptic, anti-bacterial, or other
form of mouth cleansing, hygienic, or breathening agent, or as
significant as delivering a drug (either over the counter, nutraceutical,
or prescription) that has either oral, lingual, or other biologic
activity for various medical purposes through absorption or consumption
via the oral delivery. According to one such example, for illustration
and not to limit the broad scope of the foregoing, fluid agents may be
delivered orally via these systems and methods and which may treat
certain nasal or sinus ailments or conditions.

[0171] The devices, systems and methods as described herein can thus be
applied for the treatment of various diseases and conditions other than
snoring and/or OSA. For example, the disclosed appliance and delivery
methods can be used to deliver suitable agents for the treatment of oral
hygiene and xerostomia, as well as any other treatment that can benefit
from having a stimulant applied in the manner disclosed herein.

[0172] Certain embodiments disclosed relate to delivering therapeutic
agents, such as stimulants, into the mouth via an oral device. Such
embodiments contemplate a broad scope with respect to the particular
preparation for such agents in terms of the specific type of material
(e.g. fluids, solids, etc.), as described elsewhere herein. These
alternatives include in certain regards gas preparations for therapy
delivery. However, it is also appreciated that gasses are characterized
with properties that rapidly fill a volume or space in which they are
introduced. In more detailed embodiments where isolated local delivery to
a particular part of the mouth is desired, e.g. only the anterior portion
at or adjacent the front incisor teeth, gas may be a non-ideal
preparation to optimally achieve the intended result. For example, where
anterior tongue repositioning is desired toward the front teeth, delivery
of gas at that anterior location may instead rapidly migrate toward the
posterior mouth and/or throat, and thus mitigate the local target of the
stimulus from its intended anterior location. Accordingly, it is
appreciated in certain such embodiments that a "non-gas" category of
material preparation of the agent (e.g. tongue repositioning stimulus) is
considered particularly beneficial (vs. a gas alternative).

[0173] From the description herein, it will be appreciated that methods,
devices, and systems are disclosed for controlled delivery of a therapy,
such as a stimulant, to a mouth of a subject via an oral device
positioned in a secured configuration in the mouth. At least one of a
tongue position stimulator (TST) and tongue position sensor (TSE) is
provided, according to certain aspects. According to another aspect, a
stimulus is delivered to the mouth and/or tongue via a mouthpiece secured
to the subject's teeth. In another regard, a stimulus is delivered that
generates a natural response to eliminate or reduce sleep disorders, such
as for example at least one of snoring and obstructive sleep apnea. In
certain embodiments, the therapy delivery comprises at least one of:
isolated delivery to only an anterior portion of the mouth at or adjacent
to the front incisors, a non-gas preparation of therapeutic agent, and
either via coupling an external reservoir to the oral device or coating
the therapeutic agent or stimulant onto a dispensing surface of the oral
device.

[0174] In addition to the disclosure herein, various aspects, modes,
embodiments, features, and variations disclosed hereunder are summarized
as follows.

[0175] 1. One embodiment is a method for treating sleep disorder breathing
in a sleeping individual, comprising: providing a stimulant that induces
at least one natural response within a mouth of the sleeping individual
when the stimulant enters the mouth; delivering the stimulant at a
location behind one or more teeth in the mouth to induce at least one
natural response to reduce sleep disorder breathing and improve the
ability of the sleeping individual to maintain a sleep state; and
changing delivery of the stimulant.

[0176] According to another embodiment, the changing of the delivery
comprises reducing the delivery. In another embodiment, the changing
comprises intermittent changing. In another embodiment, the delivery
reduction comprises intermittently reducing delivery.

[0177] 2. Another embodiment is the method of embodiment 1, wherein the
intermittent reduction comprises intermittently pausing the delivery of
the stimulant.

[0178] 3. Another embodiment is the method of embodiment 1, wherein the
intermittently reduced delivery temporarily ceases inducing the at least
one natural response.

[0179] 4. Another embodiment is the method of embodiment 1, wherein the
intermittently reduced delivery prevents the stimulant from waking the
individual.

[0180] 5. Another embodiment is the method of embodiment 1, wherein
providing the stimulant comprises automatically delivering the stimulant
from a supply source while the individual is in a sleep state.

[0181] 6. Another embodiment is the method of embodiment 1, wherein the
natural response comprises an activity comprising at least one of
salivation, forward movement of the tongue, repositioning of the tongue,
swallowing and a combination thereof.

[0182] 7. Another embodiment is the method of embodiment 6, wherein at
least one of the activities reduces vibrations of a soft palate or uvula
without waking the individual.

[0183] 8. Another embodiment is the method of embodiment 1, wherein
providing the stimulant includes positioning an oral appliance within the
mouth having a delivery port that delivers the stimulant to the tongue.

[0184] 9. Another embodiment is the method of embodiment 8, where
positioning the oral appliance within the mouth comprises positioning the
oral appliance on at least one of the lower front teeth such that the
delivery port of the oral appliance is directly adjacent to the posterior
side of the lower front teeth.

[0185] 10. Another embodiment is the method of embodiment 8, where
positioning the oral appliance within the mouth comprises positioning the
oral appliance on at least one of the upper front teeth such that the
delivery port of the oral appliance is directly adjacent to the posterior
side of the upper front teeth.

[0186] 11. Another embodiment is the method of embodiment 8, where the
oral appliance comprises at least one of a mandibular advancement device,
a continuous positive airway pressure device, a mouthguard, a custom
molded mouthpiece, and a retainer.

[0187] 12. Another embodiment is the method of embodiment 8, where the
oral appliance comprises an internal reservoir fluidly coupled to the
delivery port, the internal reservoir containing at least a portion of
the stimulant, and where the delivery port comprises a valve, where
providing the stimulant comprises opening of the valve to dispense the
stimulant.

[0188] 13. Another embodiment is the method of embodiment 1, where
providing the stimulant comprises providing an external reservoir
containing the stimulant.

[0189] 14. Another embodiment is the method of embodiment 1, further
comprising providing a second stimulant to trigger an olfactory response
in the sleeping individual.

[0190] 15. Another embodiment is the method of embodiment 1, where the
stimulant comprises a substance comprising a taste selected from a group
consisting of a sour taste, a citric taste, a sweet taste.

[0191] 16. Another embodiment is the method of embodiment 1, where the
stimulant comprises a taste selected from a group consisting of xylitol.

[0192] 17. Another embodiment is the method of embodiment 1, where
intermittently reducing delivery of the stimulant comprises reducing the
stimulant delivery until a triggering signal returns an increased
delivery of the stimulant.

[0193] 18. Another embodiment is the method of embodiment 17, further
comprising: a dispensing unit cooperating with a sensor; wherein the
triggering signal is generated in response to the sensor; and wherein the
dispensing unit is triggered to increase delivery of the stimulant in
response to the triggering signal.

[0194] 19. Another embodiment is the method of embodiment 17, wherein the
dispensing unit is in electrical communication with the sensor.

[0195] 20. Another embodiment is the method of embodiment 18, wherein the
sensor comprises a sensor selected from the group consisting of a
pressure sensor, an optical sensor, a sound sensor, a movement sensor, an
electro-magnetic sensor.

[0196] 21. Another embodiment is the method of embodiment 18, where the
sensor is positioned in the mouth and generates a signal based on a
movement or position of the tongue.

[0197] 22. Another embodiment is the method of embodiment 18, where the
amount of stimulant delivered is determined by the triggering signal.

[0198] 23. Another embodiment is the method of embodiment 17, further
comprising measuring a degree of tongue movement with the sensor and
using the triggering signal to determine the amount of stimulant based on
the degree of movement.

[0199] 24. Another embodiment is the method of embodiment 1, where
delivering the stimulant and intermittently reducing delivery of the
stimulant are timed with an event comprising respiration, respiratory
effect, respiratory flow, hypoxia, hypopnea, oxygen saturation, or
pausing the stimulant until a triggering signal restarts delivery of the
stimulant.

[0200] 25. Another embodiment is a method for minimizing sleep
disturbances in an individual, the method comprising: positioning a
dispensing unit within a mouth of the individual, where the dispensing
unit comprises at least one port adjacent to a tongue; providing a supply
of a stimulant through the port that induces a biological response in the
mouth of the individual; controlling delivery of the stimulant between a
first delivery phase, in which the stimulant is delivered to the mouth to
induce the biological response and a second delivery phase, during which
delivery of the stimulant to the mouth is reduced form the first delivery
phase.

[0201] 26. Another embodiment is the method of embodiment 25, wherein the
second delivery profile comprises substantially stopping delivery of the
stimulant.

[0202] 27. Another embodiment is the method of embodiment 25, wherein
controlling delivery of the stimulant permits periodically inducing the
biological response without waking the individual.

[0203] 28. Another embodiment is the method of embodiment 25, wherein
providing the supply of the stimulant comprises automatically dispensing
the stimulant while the individual is in a sleep state.

[0204] 29. Another embodiment is the method of embodiment 25, where
providing the supply of the stimulant comprises metering the stimulant to
induce the biological response without waking the patient.

[0205] 30. Another embodiment is the method of embodiment 25, further
comprising: containing at least a portion of the stimulant within an
internal reservoir of the dispensing unit that is fluidly coupled with
the port; and wherein providing the supply of the stimulant comprises
dispensing the stimulant from the internal reservoir through the port.

[0206] 31. Another embodiment is the method of embodiment 30, wherein
providing the supply of the stimulant comprises opening a valve to
dispense the stimulant from the internal reservoir through the port.

[0207] 32. Another embodiment is the method of embodiment 30, wherein the
supply of the stimulant is fully contained within the reservoir such that
the dispensing unit is fully contained within the mouth.

[0208] 33. Another embodiment is the method of embodiment 30, further
comprising providing a remainder of the stimulant in an external
reservoir that is fluidly coupled to the internal reservoir.

[0209] 34. Another embodiment is the method of embodiment 25, further
comprising: containing at least a portion of the stimulant within an
external reservoir located outside of the dispensing device and mouth and
that is fluidly coupled to the port; and delivering the stimulant
comprises dispensing of the stimulant from the external reservoir through
the port into the mouth.

[0210] 35. Another embodiment is the method of embodiment 25, wherein the
biological response comprises salivation, forward movement of the tongue,
repositioning of the tongue, swallowing, or a combination thereof.

[0211] 36. Another embodiment is the method of embodiment 25, wherein
positioning the dispensing unit within the mouth comprises positioning
the dispensing unit on at least one of the lower front teeth such that
the delivery port of the dispensing unit is directly adjacent to the
posterior side of the lower front teeth.

[0212] 37. Another embodiment is the method of embodiment 25, wherein the
dispensing unit comprises a mandibular advancement device, a continuous
positive airway pressure device, a mouthguard, custom molded mouthpiece,
or a retainer.

[0213] 38. Another embodiment is the method of embodiment 25, further
comprising providing a second stimulant to trigger an olfactory response
in the sleeping individual.

[0214] 39. Another embodiment is the method of embodiment 25, wherein the
stimulant comprises a substance comprising a taste comprising at least
one of a sour taste, a citric taste, and a sweet taste.

[0215] 40. Another embodiment is the method of embodiment 25, wherein the
stimulant comprises xylitol.

[0216] 41. Another embodiment is the method of embodiment 25, further
comprising providing a triggering signal to control delivery of the
stimulant between the first delivery phase and the second delivery phase.

[0217] 42. Another embodiment is the method of embodiment 41, further
comprising: a sensor coupled to the dispensing unit; and wherein the
triggering signal is generated in response to a parameter sensed by the
sensor.

[0218] 43. Another embodiment is the method of embodiment 42, wherein the
dispensing unit comprises the sensor.

[0219] 44. Another embodiment is the method of embodiment 42, where the
sensor comprises a pressure sensor, an optical sensor, a sound sensor, a
movement sensor, an EEG sensor, an EMG sensor, or an electro-magnetic
sensor.

[0220] 45. Another embodiment is the method of embodiment 42, further
comprising positioning the sensor in the mouth and generating a signal
based on a movement or position of the tongue or a movement or position
of the jaw.

[0221] 46. Another embodiment is the method of embodiment 42, where the
amount of stimulant delivered is determined by the triggering signal.

[0222] 47. Another embodiment is the method of embodiment 42, further
comprising: measuring a degree of tongue movement with the sensor; and
using the triggering signal to determine the amount of stimulant based on
the degree of movement.

[0223] 48. Another embodiment is the method of embodiment 42, further
comprising: measuring a degree of jaw movement with the sensor; and using
the triggering signal to determine the amount of stimulant based on the
degree of movement.

[0224] 49. Another embodiment is an oral device for dispensing a stimulant
that produces a biological response within the mouth to reduce sleep
disorder breathing in an individual, comprising: a device body having a
dental cavity for removably nesting with one or more structures within
the mouth; a dispensing port adjacent to an anterior portion of the
dental cavity, such that when the device body is positioned within a
mouth the dental cavity is adjacent to the teeth and the dispensing port
is adjacent to a posterior surface of teeth such that the stimulant
leaving the dispensing port draws the tongue adjacent or next to the
posterior surface of the teeth; and a fluid reservoir fluidly coupled to
the dispensing port and configured to contain and supply the stimulant to
the dispensing port.

[0225] 50. Another embodiment is the device of embodiment 49, wherein the
device is further configured to allow for an intermittent change in the
delivery of the stimulant from the reservoir to the mouth through the
dispensing port.

[0226] 51. Another embodiment is the device of embodiment 50, further
comprising: a valve located in a fluid path between the fluid reservoir
and the dispensing port; and wherein the valve is configured to allow
intermittently changing the delivery profile of the stimulant through the
dispensing port.

[0227] 52. Another embodiment is the device of embodiment 49, further
comprising a palatial nesting section adjacent to the dental cavity and
configured to nest within an arch of a palate to improve retention of the
device body within the mouth.

[0228] 53. Another embodiment is the device of embodiment 49, further
comprising: a control unit configured to control the intermittently
changed delivery of the stimulant.

[0229] 54. Another embodiment is the device of embodiment 53, wherein: the
control unit is in coupled communication with the valve; and the control
unit comprises a user interface to control operation of the valve.

[0230] 55. Another embodiment is the device of embodiment 51, further
comprising: at least one sensor electrically coupled to the valve; and
wherein the sensor is configured to generate a triggering signal.

[0231] 56. Another embodiment is the device of embodiment 55, wherein the
sensor comprises a pressure sensor, an optical sensor, a sound sensor, a
movement sensor, an EEG sensor, an EMG sensor, or an electro-magnetic
sensor.

[0232] 57. Another embodiment is the device of embodiment 55, wherein the
sensor is coupled to the device body in a manner such that it is located
within the mouth when the device body is positioned in the mouth.

[0233] 58. Another embodiment is the device of embodiment 57, wherein the
sensor is attached to the device body.

[0234] 59. Another embodiment is the device of embodiment 55, wherein the
sensor is spaced from the device body such that the sensor can remain
external to the mouth when the device body is positioned in the mouth.

[0235] 60. Another embodiment is a method for improving sleep quality in a
sleeping individual, comprising: providing a stimulant that induces a
natural response within the mouth of the individual when in contact with
a tongue of the individual; delivering the stimulant to the tongue in a
manner configured to induce the natural response; temporarily reducing
delivery of the stimulant in a manner configured to temporarily reduce
inducing the natural response; and returning to increased delivery of the
stimulant to again induce the natural response.

[0236] 61. Another embodiment is the method of embodiment 60, wherein
temporarily reducing delivery of the stimulant comprises ceasing delivery
of the stimulant.

[0237] 62. Another embodiment is the method of embodiment 61, wherein
returning to increased delivery of the stimulant comprises restarting
delivery of the stimulant.

[0238] 63. Another embodiment is the method of embodiment 60, further
comprising: limiting the amount of stimulant delivered to produce the
biologic activity resulting in reducing vibrations of a soft palate or
uvula without waking the individual.

[0239] 64. Another embodiment is an oral device for producing a biological
response within the mouth to reduce sleep disorder breathing in an
individual, comprising: a device body having a dental cavity for
removably nesting with one or more structures within the mouth; and a
dispensing surface adjacent to an anterior portion of the dental cavity,
such that when the device body is positioned within a mouth the dental
cavity is adjacent to the teeth and the dispensing surface is adjacent to
a posterior surface of the teeth, where the dispensing surface comprises
a supply of a stimulant, where the stimulant is releasable from the
dispensing surface over a period of time and draws a tongue adjacent to
or next to the posterior surface of the teeth.

[0240] 65. Another embodiment is a medical device system for delivering a
therapy to a mouth or tongue of a subject, comprising: an oral device
configured to be secured within the mouth in a secured configuration; a
therapy coupled to the oral device; wherein the oral device in the
secured configuration is configured to deliver the therapy into the
mouth; and at least one of:

[0241] the oral device in the secured configuration is configured to
deliver the therapy at an anterior location within the mouth,

[0242] the therapy comprises a source of therapeutic agent which is
located at an external position outside of the mouth, and a delivery
assembly is coupled to the source and also to the oral device and is
configured to deliver the agent from the source in the external position
to the oral device in the secured configuration, an active controller is
configured to actively control a delivery profile of the therapy into the
mouth via the oral device,

[0243] a sensor is coupled to a sensor location on the oral device,

[0244] the oral device comprises a palatal bridge-less mouthpiece with a
dental cavity configured to nest on at least one tooth in the mouth; and

[0245] a coating deposited on a dispensing surface of the oral device at a
delivery location, the therapy comprises a therapeutic agent contained
within the coating, and the coating is configured to release the
therapeutic agent into the mouth at the delivery location.

[0246] 66. Another embodiment is the system of embodiment 65, wherein the
oral device in the secured configuration is configured to deliver the
therapy at an anterior location within the mouth,

[0247] 67. Another embodiment is the system of embodiment 66, wherein: the
therapy comprises a source of therapeutic agent which is located at an
external position outside of the mouth; and a delivery assembly is
coupled to the source and also to the oral device and is configured to
deliver the agent from the source in the external position to the oral
device in the secured configuration.

[0248] 68. Another embodiment is the system of embodiment 67, further
comprising: an active controller that is configured to actively control a
delivery profile of the therapy into the mouth via the oral device.

[0249] 69. Another embodiment is the system of embodiment 68, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0250] 70. Another embodiment is the system of embodiment 69, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0251] 71. Another embodiment is the system of embodiment 68, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0252] 72. Another embodiment is the system of embodiment 67, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0253] 73. Another embodiment is the system of embodiment 72, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0254] 74. Another embodiment is the system of embodiment 67, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0255] 75. Another embodiment is the system of embodiment 66, further
comprising: an active controller that is configured to actively control a
delivery profile of the therapy into the mouth via the oral device at the
anterior location.

[0256] 76. Another embodiment is the system of embodiment 65, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0257] 77. Another embodiment is the system of embodiment 76, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0258] 78. Another embodiment is the system of embodiment 75, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0259] 79. Another embodiment is the system of embodiment 66, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0260] 80. Another embodiment is the system of embodiment 79, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0261] 81. Another embodiment is the system of embodiment 66, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0262] 82. Another embodiment is the system of embodiment 65, wherein: the
therapy comprises a source of therapeutic agent that is located at an
external position outside of the mouth; and a delivery assembly is
coupled to the source and also to the oral device and is configured to
deliver the agent from the source in the external position to the oral
device in the secured configuration.

[0263] 83. Another embodiment is the system of embodiment 82, further
comprising: an active controller that is coupled to the delivery assembly
and is configured to actively control a delivery profile of the delivered
agent into the mouth via the delivery assembly and oral device.

[0264] 84. Another embodiment is the system of embodiment 83, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0265] 85. Another embodiment is the system of embodiment 84, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0266] 86. Another embodiment is the system of embodiment 83, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0267] 87. Another embodiment is the system of embodiment 82, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0268] 88. Another embodiment is the system of embodiment 87, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0269] 89. Another embodiment is the system of embodiment 82, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0270] 90. Another embodiment is the system of embodiment 65, further
comprising: an active controller that is configured to actively control a
delivery profile of the therapy into the mouth via the oral device.

[0271] 91. Another embodiment is the system of embodiment 90, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0272] 92. Another embodiment is the system of embodiment 91, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0273] 93. Another embodiment is the system of embodiment 90, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0274] 94. Another embodiment is the system of embodiment 65, further
comprising: a sensor that is coupled to a sensor location on the oral
device.

[0275] 95. Another embodiment is the system of embodiment 94, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0276] 96. Another embodiment is the system of embodiment 65, wherein: the
oral device comprises a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0277] 97. A medical device system for delivering a therapy to a mouth or
tongue of a subject, comprising: a tongue position stimulator (TST)
assembly configured to deliver a stimulus to the tongue so as to
stimulate the tongue into a position; and a tongue position sensor (TSE)
assembly configured to sense a location of the tongue at the position.

[0278] 98. Another embodiment is the system of embodiment 97, further
comprising: an oral device configured to be secured within the mouth in a
secured configuration; wherein the TST comprises a stimulus coupled to
the oral device at a delivery location, and is configured to deliver the
stimulus to the mouth or tongue in the secured configuration so as to
stimulate the tongue to the position; and wherein the TSE comprises a
sensor coupled to the oral device at a sensor location and configured to
sense a tongue position corresponding with the sensor location.

[0279] 99. Another embodiment is the system of embodiment 98, further
characterized by at least one of:

[0280] the TST assembly is configured to deliver the stimulus into the
mouth at an anterior location within the mouth via the oral device in the
secured configuration;

[0281] the TST assembly further comprises a source of therapeutic agent
which comprises a stimulant, and a delivery assembly configured to couple
to the source at an external location outside the mouth and also to the
oral device in the secured configuration, and is configured to deliver
the agent from the source at the external location to the oral device in
the secured configuration in the mouth;

[0282] the TST assembly comprises an active controller that is configured
to actively control a delivery profile of the delivered agent into the
mouth via the oral device; and

[0283] the oral device comprises a palatal bridge-less mouthpiece with a
dental cavity configured to nest on at least one tooth in the mouth.

[0284] 100. Another embodiment is the system of embodiment 99, wherein:
the TST assembly is configured to deliver the therapy into the mouth at
an anterior location within the mouth via the oral device in the secured
configuration.

[0285] 101. Another embodiment is the system of embodiment 99, wherein the
TST assembly further comprises: a source of therapeutic agent which
comprises a stimulant; and a delivery assembly configured to couple to
the source at an external location outside the mouth and also to the oral
device in the secured configuration, and is configured to deliver the
agent from the source at the external location to the oral device in the
secured configuration in the mouth.

[0286] 102. Another embodiment is the system of embodiment 99, wherein the
TST assembly further comprises: an active controller that is configured
to actively control a delivery profile of the delivered agent into the
mouth via the oral device.

[0287] 103. Another embodiment is the system of embodiment 99, wherein the
oral device comprises: a palatal bridge-less mouthpiece with a dental
cavity configured to nest on at least one tooth in the mouth.

[0288] 104. Other embodiments comprise the systems of any one of
embodiments 65-103, wherein the oral device is configured to be
permanently or semi-permanently implanted in the secured configuration in
the mouth.

[0289] 105. Other embodiments comprise the systems of any one of
embodiments 65-103, wherein the oral device is configured to be
temporarily implanted in the secured configuration mouth and is removable
from the secured configuration.

[0290] 106. Other embodiments comprise the systems of any one of
embodiments 65-103, wherein the oral device comprises a mouthpiece with
at least one wall defining at least one dental cavity that is configured
to nest on at least one tooth in the mouth.

[0291] 107. Another embodiment is the system of embodiment 106, wherein
the mouthpiece comprises at least two opposite walls with a space
therebetween, said space defining at least in part the dental cavity.

[0292] 108. Another embodiment is the system of embodiment 106, wherein
the at least one dental cavity is configured to nest on multiple teeth in
the mouth.

[0293] 109. Another embodiment is the system of embodiment 108, wherein
the mouthpiece is molded to form-fit onto the teeth of the subject.

[0294] 110. Another embodiment is the system of embodiment 106, wherein
the at least one tooth comprises an incisor.

[0295] 111. Another embodiment is the system of any one of embodiments
65-103, wherein: the therapy comprises a source of therapeutic agent; a
first delivery port is located at a first port location on the oral
device coinciding at or adjacent to an incisor in the secured
configuration; and the therapeutic agent is coupled for delivery into the
mouth at the first delivery port.

[0296] 112. Another embodiment is the system of embodiment 111, wherein
the first port location coincides at or adjacent to at least one of the
two middle incisors in the front of the mouth.

[0297] 113. Another embodiment is the system of embodiment 111, wherein:
the source comprises a reservoir; the therapeutic agent comprises a
volume of a fluid material; and a delivery tube is fluidly coupled to the
reservoir and also to the delivery port so as to provide for fluid
delivery of the fluid material from the reservoir to the delivery port.

[0298] 114. Other embodiments comprise the systems of any one of
embodiments 65-103, wherein the therapy comprises a stimulant.

[0299] 115. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a delivered energy.

[0300] 116. Another embodiment is the system of embodiment 115, wherein
the delivered energy comprises electricity.

[0301] 117. Another embodiment is the system of embodiment 116, wherein
the delivered energy comprises an RF current.

[0302] 118. Another embodiment is the system of embodiment 115, wherein
the delivered energy comprises thermal energy.

[0303] 119. Another embodiment is the system of embodiment 115, wherein
the delivered energy comprises light energy.

[0304] 120. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a cryogenic cooling stimulant.

[0305] 121. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a material.

[0306] 122. Another embodiment is the system of embodiment 121, wherein
the material comprises a fluid.

[0307] 123. Another embodiment is the system of embodiment 122, wherein
the fluid comprises a liquid.

[0308] 124. Another embodiment is the system of embodiment 122, wherein
the fluid comprises a gas.

[0309] 125. Another embodiment is the system of embodiment 121, wherein
the material comprises a flavor.

[0310] 126. Another embodiment is the system of embodiment 121, wherein
the material comprises a taste.

[0311] 127. Another embodiment is the system of embodiment 121, wherein
the material comprises a smell.

[0312] 128. Another embodiment is the system of embodiment 121, wherein
the material comprises a liquid taste stimulant.

[0313] 129. Another embodiment is the system of embodiment 121, wherein
the material comprises a sweet taste.

[0314] 130. Another embodiment is the system of embodiment 129, wherein
the sweet taste comprises a sugar, or a pre-cursor, analog, or derivative
thereof.

[0315] 131. Another embodiment is the system of embodiment 130, wherein
the sugar comprises xylitol, or a pre-cursor, analog, or derivative
thereof.

[0316] 132. Another embodiment is the system of embodiment 130, wherein
the material comprises a liquid.

[0317] 133. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a mechanical stimulant.

[0318] 134. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a texture stimulant.

[0319] 135. Another embodiment is the system of embodiment 114, wherein
the stimulant comprises a tongue stimulant characterized as stimulating a
tongue repositioning activity in response to exposure to the stimulant.

[0320] 136. Other embodiments include the systems of any of embodiments
65-66, 75-81, 90-98, or 100-103, wherein: the therapy comprises a source
of therapeutic agent; the source comprises a reservoir; and the
therapeutic agent comprises a therapeutic material within the reservoir.

[0321] 137. Another embodiment is the system of embodiment 136, wherein:
the reservoir is located in the oral device.

[0322] 138. Another embodiment is the system of embodiment 136, wherein:
the reservoir is located separately from the oral device at an external
location outside the mouth when the oral device is in the secured
configuration; and a delivery assembly is coupled to the reservoir and
also to the oral device and is configured to deliver the therapeutic
material from the reservoir in the external location to the mouth via the
oral device in the secured configuration.

[0323] 139. Other embodiments include the systems of any of embodiments
65-103, wherein: the therapy comprises a source of therapeutic agent; and
the active controller comprises a pump coupled to a reservoir containing
the therapeutic agent and that is configured to pump the agent according
to the controlled delivery profile into the mouth via the oral device.

[0324] 140. Other embodiments include the systems of any of embodiments
65-103, wherein the controlled delivery profile comprises a constant
delivery rate of the therapy over a time period.

[0325] 141. Another embodiment is the system of embodiment 140, wherein
the time period is configured to coincide with a sleep period for the
subject.

[0326] 142. Other embodiments include the systems of any one of
embodiments 65-103, wherein the controlled delivery profile comprises a
changing delivery rate of the therapy over time between at least a first
rate and a second rate that is below the first rate.

[0327] 143. Another embodiment is the system of embodiment 142, wherein
the time period is configured to coincide with a sleep period for the
subject.

[0328] 144. Another embodiment is the system of embodiment 142, wherein
the changing delivery rate comprises a cycle between the first and second
rates over the time.

[0329] 145. Another embodiment is the system of embodiment 144, wherein
the first and second rates comprise on and off conditions.

[0330] 146. Another embodiment is the system of embodiment 145, wherein
the on and off conditions are relative to a threshold for achieving a
therapeutic result in the subject, such that the first rate comprising
the on condition is above the threshold, and the second rate comprising
the off condition is below the threshold.

[0331] 147. Another embodiment is the system of embodiment 146, wherein
the second rate comprising the off condition comprises a substantially
zero rate and non-delivery of the therapy.

[0332] 148. Another embodiment is the system of embodiment 146, wherein
the second rate comprising the off condition comprises a non-zero rate of
delivering the therapy below the threshold.

[0333] 149. Another embodiment is the system of embodiment 144, wherein
the cycle comprises a substantial step cycle between the first and second
rates.

[0334] 150. Another embodiment is the system of embodiment 145, wherein
the cycle comprises a ramping cycle between the first and second rates.

[0335] 151. Other embodiments include the systems of any of embodiments
65-103, wherein the active controller further comprises: a driver for
driving the delivery of the therapy to the oral device; an input set of
instructions for controlling the delivery according to the controlled
delivery profile, and a processor configured to receive the input set of
instructions and coupled to the driver to actuate the driver to drive the
delivery of the therapy according to the instructions.

[0336] 152. Another embodiment is the system of embodiment 151, wherein
the processor is configured to receive the set of instructions at least
in part by a manual input by a user of the system.

[0337] 153. Another embodiment is the system of embodiment 151, further
comprising: a software program embedded in a non-transitory computer
readable medium that contains the at least a portion of the set of
instructions; wherein the processor is configured to run the software
program to receive at least the portion of the set of instructions.

[0338] 154. Another embodiment is the system of embodiment 153, wherein
the active controller further comprises a sensor input configured to
receive sensed information from a sensor coupled to the subject, and the
set of instructions are variable in response to the sensed information
received.

[0339] 155. Another embodiment is the system of embodiment 154, wherein
the sensed information relates to a tongue position in the mouth of the
subject.

[0340] 156. Other embodiments include the systems of any of embodiments
65-103, further comprising: a light source optically coupled to transmit
an illumination light signal into the mouth at an illumination port on
the oral device; and wherein the sensor comprises an optical sensor
configured to sense a reflected light signal reflected in the mouth from
the illumination light signal transmitted into the mouth.

[0341] 157. Another embodiment is the system of embodiment 156, wherein
the sensor is configured to sense a position of the tongue against the
sensor location based at least in part upon a change in light from the
light source that is reflected from the first end.

[0342] 158. Other embodiments include the systems of any of embodiments
65-103, wherein the sensor comprises a pressure sensor.

[0343] 159. Another embodiment is the system of embodiment 158, wherein
the pressure sensor comprises an optical pressure sensor.

[0344] 160. Another embodiment is the system of embodiment 158, wherein
the pressure sensor comprises a pneumatic or hydraulic pressure sensor.

[0345] 161. Another embodiment is the system of embodiment 158, wherein
the pressure sensor comprises a strain gauge pressure sensor.

[0346] 162. Other embodiments include the systems of any of embodiments
65-103, wherein the sensor is configured to sense a position of the
tongue in the mouth.

[0347] 163. Another embodiment is the system of embodiment 162, wherein
the position comprises an anterior portion of the mouth.

[0348] 164. Another embodiment is the system of embodiment 163, wherein
the anterior position is at or adjacent to the front incisors in the
mouth.

[0349] 165. Another embodiment is the system of embodiment 164, wherein
the anterior position is at or adjacent to the front top incisors in the
mouth.

[0350] 166. Other embodiments include the systems of any of embodiments
65-103, wherein the sensor is configured to sense an applied force at the
sensor location.

[0351] 167. Another embodiment is the system of embodiment 166, wherein
the sensor location is on a lingual side of the teeth, and the applied
force is from the tongue.

[0352] 168. Other embodiments include the system of any of embodiments
65-103, wherein: the oral device comprises a mouthpiece with at least one
dental cavity configured to nest on multiple teeth in the mouth
comprising at least the two middle front incisors; the source of
therapeutic agent comprises a reservoir containing a volume of fluid
flavor, taste, or smell stimulant; the delivery assembly comprises a
fluid delivery tube that is fluidly coupled to the reservoir at the
external location outside of the mouth and also to a delivery port
located at a delivery port location on the mouthpiece coinciding with at
least one of the incisor teeth in the secured configuration; and the
active controller comprises a pump configured to actively control a
delivery profile of the stimulant from the reservoir via the delivery
assembly to the mouthpiece and through the delivery port into the mouth.

[0353] 169. Another embodiment is the system of embodiment 168, and
further wherein; the therapy comprises a stimulated repositioning of the
tongue to the anterior location in response to the controlled delivery of
the stimulant into the mouth.

[0354] 170. Another embodiment is a method for delivering a therapy to a
mouth or tongue of a subject, comprising: securing an oral device within
the mouth in a secured configuration; coupling a therapy to the oral
device; delivering the therapy into the mouth via the oral device; and at
least one of:

[0355] delivering the therapy at an anterior location within the mouth via
the oral device in the secured configuration,

[0356] providing a source of a therapeutic agent at an external position
outside of the mouth, coupling the source in the external position to the
oral device in the secured configuration via a delivery assembly, and
delivering the agent from the source in the external position to the oral
device in the secured configuration via the delivery assembly,

[0357] actively controlling a delivery profile of the therapy into the
mouth via the oral device in the secured configuration,

[0358] sensing a parameter within the mouth with a sensor at a sensor
location on the oral device in the secured configuration;

[0359] securing the oral device in the secured configuration by nesting a
dental cavity of a palatal bridge-less mouthpiece on at least one tooth
in the mouth; and

[0360] coupling the therapy to the oral device by coating a therapeutic
agent onto a dispensing surface of the oral device, and delivering the
therapy into the mouth by releasing the therapeutic agent into the mouth
via the coating.

[0361] 171. Another embodiment is the method of embodiment 170, further
comprising: delivering the therapy at an anterior location within the
mouth via the oral device in the secured configuration.

[0362] 172. Another embodiment is the method of embodiment 171, further
comprising: positioning a source of therapeutic agent at an external
position outside of the mouth; and coupling the source to the oral device
in the secured configuration via a delivery assembly; and delivering the
therapy by delivering the agent from the source in the external position
to the oral device in the secured configuration via the delivery
assembly.

[0363] 173. Another embodiment is the method of embodiment 172, further
comprising: actively controlling a delivery profile of the therapy into
the mouth via the oral device in the secured configuration.

[0364] 174. Another embodiment is the method of embodiment 173, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0365] 175. Another embodiment is the method of embodiment 174, further
comprising: securing the oral device in the secured configuration by
nesting a dental cavity of a palatal bridge-less mouthpiece on at least
one tooth in the mouth.

[0366] 176. Another embodiment is the method of embodiment 173, further
comprising: securing the oral device in the secured configuration by
nesting a dental cavity of a palatal bridge-less mouthpiece on at least
one tooth in the mouth.

[0367] 177. Another embodiment is the method of embodiment 172, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0368] 178. Another embodiment is the method of embodiment 177, further
comprising: securing the oral device in the secured configuration by
nesting a dental cavity of a palatal bridge-less mouthpiece on at least
one tooth in the mouth.

[0369] 179. Another embodiment is the method of embodiment 172, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0370] 180. Another embodiment is the method of embodiment 171, further
comprising: actively controlling a delivery profile of the therapy into
the mouth via the oral device in the secured configuration.

[0371] 181. Another embodiment is the method of embodiment 170, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0372] 182. Another embodiment is the method of embodiment 181, further
comprising: securing the oral device in the secured configuration by
nesting a dental cavity of a palatal bridge-less mouthpiece on at least
one tooth in the mouth.

[0373] 183. Another embodiment is the method of embodiment 180, further
comprising: securing the oral device in the secured configuration by
nesting a dental cavity of a palatal bridge-less mouthpiece on at least
one tooth in the mouth.

[0374] 184. Another embodiment is the method of embodiment 171, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0375] 185. Another embodiment is the method of embodiment 184, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0376] 186. Another embodiment is the method of embodiment 171, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0377] 187. Another embodiment is the method of embodiment 170, wherein:

[0378] positioning a source of therapeutic agent at an external position
outside of the mouth; and coupling the source to the oral device in the
secured configuration via a delivery assembly; and delivering the therapy
by delivering the agent from the source in the external position to the
oral device in the secured configuration via the delivery assembly.

[0379] 188. Another embodiment is the method of embodiment 187, further
comprising: actively controlling a delivery profile of the therapy into
the mouth via the oral device in the secured configuration.

[0380] 189. Another embodiment is the method of embodiment 188, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0381] 190. Another embodiment is the method of embodiment 189, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0382] 191. Another embodiment is the method of embodiment 188, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0383] 192. Another embodiment is the method of embodiment 187, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0384] 193. Another embodiment is the method of embodiment 192, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0385] 194. Another embodiment is the method of embodiment 187, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0386] 195. Another embodiment is the method of embodiment 170, further
comprising: actively controlling a delivery profile of the therapy into
the mouth via the oral device in the secured configuration.

[0387] 196. Another embodiment is the method of embodiment 195, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0388] 197. Another embodiment is the method of embodiment 196, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0389] 198. Another embodiment is the method of embodiment 195, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0390] 199. Another embodiment is the method of embodiment 170, further
comprising: sensing a parameter within the mouth with a sensor at a
sensor location on the oral device in the secured configuration.

[0391] 200. Another embodiment is the method of embodiment 199, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0392] 201. Another embodiment is the method of embodiment 170, wherein:
securing the oral device in the secured configuration by nesting a dental
cavity of a palatal bridge-less mouthpiece on at least one tooth in the
mouth.

[0393] 202. A method for delivering a therapy to a mouth or tongue of a
subject, comprising: delivering a stimulus to the tongue via a tongue
position stimulator (TST) assembly; stimulating the tongue into a
position by delivering the stimulus; and sensing a location of the tongue
at the position via a tongue position sensor (TSE) assembly.

[0394] 203. Another embodiment is the method of embodiment 202, further
comprising: securing an oral device within the mouth in a secured
configuration; wherein the TST assembly delivers the stimulus at a
delivery location on the oral device in the secured configuration; and
wherein the TSE assembly senses the tongue location at the position via a
sensor coupled to the oral device at a sensor location corresponding with
the position in the secured configuration.

[0395] 204. Another embodiment is the method of embodiment 203, wherein
delivering the stimulus via the TST is further characterized by at least
one of:

[0396] delivering the stimulus at an anterior location within the mouth
via the oral device in the secured configuration;

[0397] coupling a source of therapeutic agent comprising a stimulant at an
external location outside the mouth to the oral device in the secured
configuration via a delivery assembly, and delivering the agent with the
delivery assembly from the source at the external location and to the
oral device in the secured configuration and into the mouth;

[0398] actively controlling a delivery profile of the delivered agent into
the mouth via the oral device in the secured configuration;

[0399] securing the oral device in the secured configuration by nesting
dental cavity of a palatal bridge-less mouthpiece on at least one tooth
in the mouth; and

[0400] coating the therapeutic agent onto a dispensing surface of the oral
device, and releasing the therapeutic agent from the coating into the
mouth.

[0401] 205. Another embodiment is the method of embodiment 204, wherein
delivering the stimulus via the TST is further characterized by:
delivering the stimulus at an anterior location within the mouth via the
oral device in the secured configuration.

[0402] 206. Another embodiment is the method of embodiment 204, wherein
delivering the stimulus via the TST is further characterized by: coupling
a source of therapeutic agent comprising a stimulant at an external
location outside the mouth to the oral device in the secured
configuration via a delivery assembly; and delivering the agent with the
delivery assembly from the source at the external location and to the
oral device in the secured configuration and into the mouth.

[0403] 207. Another embodiment is the method of embodiment 204, wherein
delivering the stimulus via the TST is further characterized by: actively
controlling a delivery profile of the delivered agent into the mouth via
the oral device in the secured configuration.

[0404] 208. Another embodiment is the method of embodiment 204, wherein
delivering the stimulus via the TST is further characterized by: securing
the oral device in the secured configuration by nesting dental cavity of
a palatal bridge-less mouthpiece on at least one tooth in the mouth.

[0405] 209. Other embodiments include the methods of any of embodiments
170-208, further comprising: permanently or semi-permanently implanting
the oral device in the secured configuration in the mouth.

[0406] 210. Other embodiments include the methods of any of embodiments
170-208, further comprising: removably securing the oral device in the
secured configuration during a sleep period; and removing the removably
secured oral device from the secured configuration following termination
of the sleep period.

[0407] 211. Other embodiments include the methods of any of embodiments
170-208, further comprising: securing the oral device in the secured
configuration in the mouth by nesting at least one wall defining at least
one dental cavity on at least one tooth in the mouth.

[0408] 212. Another embodiment is the method of embodiment 211, further
comprising: positioning the at least one tooth within at least one space
between at least two opposite walls defining at least in part the dental
cavity.

[0409] 213. Another embodiment is the method of embodiment 211, further
comprising nesting the at least one wall defining the at least one dental
cavity on multiple teeth in the mouth.

[0410] 214. Another embodiment is the method of embodiment 213, further
comprising molding a mouthpiece to form-fit onto the multiple teeth.

[0411] 215. Another embodiment is the method of embodiment 211, wherein
the at least one tooth comprises an incisor.

[0412] 216. Another embodiment is the method of any one of embodiments
170-208 above, wherein delivering the therapy via the TST assembly is
further characterized by: providing a source of therapeutic agent;
positioning a first delivery port that is located at a first port
location on the oral device to coincide at or adjacent to an incisor in
the secured configuration; and coupling the therapeutic agent to the
first delivery port and delivering the agent through the first delivery
port at the first port location in the secured configuration.

[0413] 217. Another embodiment is the method of embodiment 216, further
comprising: positioning the first port location to coincide at or
adjacent to at least one of the two middle incisors in the front of the
mouth in the secured configuration.

[0414] 218. Another embodiment is the method of embodiment 216, wherein
delivering the therapy via the TST is further characterized by: providing
the source of therapeutic agent in a reservoir; providing the therapeutic
agent as a volume of a fluid material; and fluidly coupling the reservoir
to the delivery port via a delivery passageway therebetween; and causing
the fluid material to flow from the reservoir, along the delivery
passageway, and through the delivery port into the mouth.

[0415] 219. Other embodiments include the methods of any of embodiments
170-208, wherein delivering the therapy comprises delivering a stimulant.

[0416] 220. Another embodiment is the method of embodiment 219, wherein
the delivering the stimulant comprises delivering energy.

[0417] 221. Another embodiment is the method of embodiment 220, wherein
delivering the energy comprises delivering an electrical current.

[0418] 222. Another embodiment is the method of embodiment 221, wherein
the delivered the electrical current comprises delivering a
radiofrequency (RF) current.

[0421] 225. Another embodiment is the method of embodiment 219, wherein
delivering the stimulant comprises delivering a cryogenic cooling
stimulant.

[0422] 226. Another embodiment is the method of embodiment 219, wherein
delivering the stimulant comprises delivering a material.

[0423] 227. Another embodiment is the method of embodiment 226, wherein
the delivering the material comprises delivering a fluid.

[0424] 228. Another embodiment is the method of embodiment 227, wherein
delivering the fluid comprises delivering a liquid.

[0425] 229. Another embodiment is the method of embodiment 227, wherein
delivering the fluid comprises delivering a gas.

[0426] 230. Another embodiment is the method of embodiment 226, wherein
delivering the material comprises delivering a flavor.

[0427] 231. Another embodiment is the method of embodiment 226, wherein
delivering the material comprises delivering a taste.

[0428] 232. Another embodiment is the method of embodiment 226, wherein
delivering the material comprises delivering a smell.

[0429] 233. Another embodiment is the method of embodiment 226, wherein
delivering the material comprises delivering a liquid taste stimulant.

[0430] 234. Another embodiment is the method of embodiment 226, wherein
delivering the material comprises delivering a sweet taste.

[0431] 235. Another embodiment is the method of embodiment 234, wherein
delivering the sweet taste comprises delivering a sugar, or a pre-cursor,
analog, or derivative thereof.

[0432] 236. Another embodiment is the method of embodiment 235, wherein
delivering the sugar comprises delivering xylitol, or a pre-cursor,
analog, or derivative thereof.

[0433] 237. Another embodiment is the method of embodiment 235, wherein
delivering the material comprises delivering a liquid.

[0434] 238. Another embodiment is the method of embodiment 219, wherein
the delivering the stimulant comprises providing a mechanical stimulant.

[0435] 239. Another embodiment is the method of embodiment 219, wherein
delivering the stimulant comprises delivering a texture stimulant.

[0436] 240. Another embodiment is the method of embodiment 219, wherein
delivering the stimulant comprises delivering a tongue stimulant
characterized as stimulating a tongue repositioning activity in response
to exposure to the stimulant.

[0437] 241. Another embodiment is a method of any one of embodiments
170-171, 180-186, 195-203, or 205-208 above, further comprising:
providing a source of therapeutic agent which comprises a therapeutic
material in a reservoir; delivering the therapy is further characterized
by delivering the therapeutic material from the reservoir into the mouth
via the oral device in the secured configuration.

[0438] 242. Another embodiment is the method of embodiment 241, further
comprising: positioning the reservoir in the oral device and in the mouth
in the secured configuration.

[0439] 243. Another embodiment is the method of embodiment 241, further
comprising: positioning the reservoir to be located separately from the
oral device at an external location outside the mouth when the oral
device is in the secured configuration; and using a delivery assembly to
couple the externally positioned reservoir to the oral device, and to
deliver the therapeutic material from the reservoir in the external
location to the mouth via the oral device, while the oral device is in
the secured configuration.

[0440] 244. Other embodiments include the methods of any of embodiments
170-208, further comprising: providing the therapy to comprise a source
of therapeutic agent in a reservoir; and coupling a pump to an active
controller and also to the reservoir; actively controlling the pump via
the active controller to deliver the agent with a controlled delivery
profile from the reservoir and to the oral device in the secured
configuration and into the mouth.

[0441] 245. Other embodiments include the methods of any of embodiments
170-208, further comprising: delivering the therapy with a controlled
delivery profile which comprises a constant delivery rate of the therapy
over a time period.

[0442] 246. Another embodiment is the method of embodiment 245, further
comprising configuring the time period to coincide with a sleep period
for the subject.

[0443] 247. Other embodiments include the methods of any of embodiments
170-208, further comprising: delivering the therapy with a controlled
delivery profile that comprises a changing delivery rate of the therapy
over time between at least a first rate and a second rate that is below
the first rate.

[0444] 248. Another embodiment is the method of embodiment 247, further
comprising configuring the time period to coincide with a sleep period
for the subject.

[0445] 249. Another embodiment is the method of embodiment 247, further
comprising configuring the changing delivery rate to comprise a cycle
between the first and second rates over the time.

[0446] 250. Another embodiment is the method of embodiment 249, further
comprising configuring the first and second rates to comprise on and off
conditions, respectively.

[0447] 251. Another embodiment is the method of embodiment 250, further
comprising configuring the on and off conditions relative to a therapy
delivery threshold for achieving a therapeutic result in the subject,
such that the first rate comprising the on condition is configured to
comprise delivering the therapy above the threshold, and the second rate
comprising the off condition is configured to comprise delivering the
therapy below the threshold.

[0448] 252. Another embodiment is the method of embodiment 251, wherein
the off condition of the second rate comprises a substantially zero rate
and non-delivery of the therapy.

[0449] 253. Another embodiment is the method of embodiment 251, wherein
the off condition of the second rate comprises a non-zero rate of therapy
delivery that is below the threshold.

[0450] 254. Another embodiment is the method of embodiment 249, wherein
the cycle comprises a substantial step cycle between the first and second
rates.

[0451] 255. Another embodiment is the method of embodiment 250, wherein
the cycle comprises a ramping cycle between the first and second rates.

[0452] 256. Other embodiments include the methods of any of embodiments
170-208, wherein actively controlling the therapy delivery is further
characterized by: using a driver for driving the delivery of the therapy
to the oral device; providing an input set of instructions for
controlling the delivery according to the controlled delivery profile,
configuring a processor to receive the input set of instructions; and
coupling the processor to the driver to actuate the driver to drive the
delivery of the therapy according to the instructions.

[0453] 257. Another embodiment is the method of embodiment 256, further
comprising manually inputting the instructions to the processor.

[0454] 258. Another embodiment is the method of embodiment 256, further
comprising: providing a software program embedded in a non-transitory
computer readable medium and that comprises at least a portion of the set
of instructions; and configuring the processor to run the software
program to receive at least the portion of the set of instructions.

[0455] 259. Another embodiment is the method of embodiment 258, further
comprising providing or receiving sensed information from a sensor
coupled to the subject, and varying the set of instructions in response
to the sensed information received.

[0456] 260. Another embodiment is the method of embodiment 259, wherein
the sensed information relates to a tongue position in the mouth of the
subject.

[0457] 261. Other embodiments include the methods of any of embodiments
170-208, further comprising: transmitting a light signal into the mouth
from a light source optically coupled to an illumination port on the oral
device; and sensing a reflected light signal reflected in the mouth from
the illumination light signal transmitted into the mouth via a light
sensor at a sensor location on the oral device.

[0458] 262. Another embodiment is the method of embodiment 261, wherein
the sensing comprises sensing a position of the tongue against the sensor
location based at least in part upon a change in light from the light
source that is reflected at the sensor location.

[0459] 263. Other embodiments include the methods of any of embodiments
170-208, wherein the sensing comprises a sensing a pressure with a
pressure sensor.

[0460] 264. Another embodiment is the method of embodiment 263, wherein
the pressure sensor comprises an optical pressure sensor.

[0461] 265. Another embodiment is the method of embodiment 263, wherein
the pressure sensor comprises a pneumatic or hydraulic pressure sensor.

[0462] 266. Another embodiment is the method of embodiment 263, wherein
the pressure sensor comprises a strain gauge pressure sensor.

[0463] 267. Other embodiments include the methods of any of embodiments
170-208, further comprising sensing a position of the tongue in the
mouth.

[0464] 268. Another embodiment is the method of embodiment 267, wherein
the position comprises an anterior portion of the mouth.

[0465] 269. Another embodiment is the method of embodiment 268, wherein
the anterior position is at or adjacent to the front incisors in the
mouth.

[0466] 270. Another embodiment is the method of embodiment 269, wherein
the anterior position is at or adjacent to the front top incisors in the
mouth.

[0467] 271. Other embodiments include the methods of any of embodiments
170-208, further comprising sensing an applied force at a sensor location
in the mouth.

[0468] 272. Another embodiment is the method of embodiment 271, wherein
the sensor location is on a lingual side of the teeth, and the applied
force is from the tongue.

[0469] 273. Another embodiment is the method of any one of embodiments
170-208, further comprising: nesting at least one dental cavity of a
mouthpiece of the oral device on multiple teeth comprising at least the
two middle front incisors in the mouth; providing a source of therapeutic
agent to comprise a volume of fluid flavor, taste, or smell stimulant
material in a reservoir positioned at an external location outside of the
mouth; using a fluid delivery tube to fluidly couple the reservoir at the
external location outside of the mouth to a delivery port located at a
delivery port location on the mouthpiece coinciding with at least one of
the incisor teeth in the secured configuration; and actively controlling
the therapy delivery via a controlled pump with a delivery profile of
stimulant from the reservoir via the delivery assembly to the mouthpiece
and through the delivery port into the mouth.

[0470] 274. Another embodiment is the method of embodiment 273, wherein
delivering the therapy further comprises; stimulating a repositioning of
the tongue to the anterior location in response to the controlled
delivery of the stimulant into the mouth.

[0471] 275. Another embodiment is a method of any of embodiments 170-208,
further comprising: treating a sleep disorder with the therapy delivery.

[0472] 276. Another embodiment is the method of embodiment 275, wherein
treating the sleep disorder comprises treating obstructive sleep apnea or
snoring with the therapy delivery.

[0473] 277. Other embodiments include the method, device, and system
embodiments elsewhere herein described, but includes constant or near
constant delivery of the fluid or material containing the stimulant, but
diluting or adjusting the stimulant in the fluid or material so that the
response is insufficient to wake the individual. For example, in cases
where the stimulant is a taste, smell, or flavor stimulant, the stimulant
can be diluted in a solution where the concentration is held high enough
to cause the desired response but low enough to avoid waking the patient
and is continuously delivered over a period of time. This stimulant
concentration in the delivery vehicle (e.g. fluid or other material), or
conversely its dilution, may be varied over time to change the stimulant
component being delivered, and thus biologic stimulation, as considered
consistent with and falling within the other aspects of the present
disclosure exemplified by the detailed embodiments.

[0474] 288. Another embodiment is a method for treating sleep disorder
breathing in a sleeping individual, the method comprising: providing a
stimulant that induces at least one natural response within a mouth of
the sleeping individual when the stimulant enters the mouth; delivering
the stimulant at a location posteriorly adjacent to one or more teeth in
the mouth to induce at least one natural response to reduce sleep
disorder breathing and improve the ability of the sleeping individual to
maintain a sleep state; and controlling delivery of the stimulant, where
controlling delivery prevents the stimulant from waking the individual.

[0475] 289. Another embodiment is the method of embodiment 288, further
comprising actively controlling the stimulant delivery with an active
controller.

[0476] 290. Another embodiment is a method for minimizing sleep
disturbances in an individual, the method comprising: positioning a
dispensing unit within a mouth of the individual, where the dispensing
unit comprises at least one port adjacent to a tongue; providing a supply
of a stimulant through the port that induces a biological response in the
mouth of the individual; controlling delivery of the stimulant; and
wherein the controlled delivery of the stimulant is configured to induce
the biological response without waking the individual.

[0477] 291. Another embodiment is an oral dispensing device for dispensing
a stimulant that produces a biological response within a mouth or airway
to reduce sleep disorder breathing in an individual, the oral dispensing
device comprising: a supply of a stimulant solution comprising a
stimulant at a concentration configured to cause a biological response
when the stimulant solution is delivered in the mouth above a threshold
delivery rate; a device body having a dental cavity for removably nesting
with one or more structures within the mouth; a dispensing port adjacent
to an anterior portion of the dental cavity, such that when the device
body is positioned within a mouth the dental cavity is adjacent to the
teeth and the dispensing port is adjacent to a posterior surface of teeth
such that the stimulant solution leaving the dispensing port draws the
tongue adjacent or next to the posterior surface of the teeth; a fluid
reservoir fluidly coupled to the dispensing port and configured to
maintain a supply of the stimulant solution; and wherein the stimulant in
the stimulant solution is also diluted sufficiently to avoid waking the
patient when continuously delivered over a period of time.

[0478] 292. Another embodiment is a method for causing a natural response
in an individual to maintain a sleep state, the method comprising:
providing a stimulant that induces a physiological response within a
mouth, throat, or airway of the individual where the physiological
response causes a change in the individual to maintain or improve a state
of sleep; delivering the stimulant in the mouth to induce the
physiological response; and controlling an amount of the stimulant that
is delivered to allow the individual to maintain the sleep state.

[0479] 293. Another embodiment is the method of embodiment 292, wherein
delivering the stimulant comprises delivering the stimulant at a location
behind one or more teeth in the mouth.

[0480] 294. Another embodiment is a method for improving sleep for an
individual, the method comprising: providing a stimulant that induces a
physiological response within a mouth, throat, or airway of the
individual; delivering the stimulant at a location behind one or more
teeth in the mouth to induce the physiological response; and controlling
an amount of the stimulant that is delivered to allow the individual to
maintain a sleep state.

[0481] 295. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, wherein a
physiological response is stimulated which comprises a degree of tongue
movement and/or increased tongue muscle tone that is sufficient to open
the airway to reduce an incidence of sleep disorder breathing.

[0482] 296. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, wherein a
physiological response is stimulated which comprises swallowing.

[0483] 297. Another embodiment is the method, device, or system of
embodiment 296 above, wherein at least one of a rate or volume of fluid
delivery and a degree of stimulated salivation is sufficient to cause the
individual or subject to swallow.

[0484] 298. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, wherein providing
the stimulant comprises automatically delivering the stimulant from a
supply source while the individual is in the sleep state.

[0485] 299. Another embodiment is the method, device, or system of any of
the other embodiments elsewhere disclosed herein, such as for example the
numbered embodiments above or below, wherein a physiological response is
stimulated that reduces vibrations of a soft palate or uvula without
waking the individual.

[0486] 300. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, wherein providing
the stimulant includes positioning an oral appliance within the mouth
having a delivery port that delivers the stimulant to the tongue.

[0487] 301. Another embodiment is the method, device, or system of any of
the other oral appliance embodiments elsewhere disclosed herein, such as
for example the numbered embodiments above or below, wherein positioning
the oral appliance within the mouth comprises positioning the oral
appliance on at least one of the lower front teeth such that the delivery
port of the oral appliance is directly adjacent to the posterior side of
the upper front teeth.

[0488] 302. Another embodiment is the method, device, or system of any of
the other oral appliance embodiments elsewhere disclosed herein, such as
for example the numbered embodiments above or below, wherein positioning
the oral appliance within the mouth comprises positioning the oral
appliance on at least one of the upper front teeth such that the delivery
port of the oral appliance is directly adjacent to the posterior side of
the upper front teeth.

[0489] 303. Another embodiment is the method, device, or system of any of
the other oral appliance embodiments elsewhere disclosed herein, such as
for example the numbered embodiments above or below, wherein the oral
appliance comprises at least one of a mandibular advancement device, a
continuous positive airway pressure device, a mouthguard, a custom molded
mouthpiece, and a retainer.

[0490] 304. Another embodiment is the method, device, or system of any of
the other oral appliance stimulant delivery embodiments elsewhere
disclosed herein, such as for example the numbered embodiments above or
below, where the oral appliance comprises an internal reservoir coupled
to a dispensing or delivery port, the internal reservoir containing at
least a portion of the stimulant.

[0491] 305. Another embodiment is the embodiment 304 above, further
comprising a valve, wherein providing the stimulant comprises opening of
the valve to dispense the stimulant.

[0492] 306. Another embodiment is the embodiment of 305 above, wherein the
delivery port comprises the valve.

[0493] 307. Another embodiment is the embodiment of 305 above, wherein the
reservoir is fluidly coupled to the dispensing or delivery port, and the
stimulant comprises a fluid.

[0494] 308. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, where providing
the stimulant comprises providing an external reservoir containing the
stimulant.

[0495] 309. Another embodiment is the method, device, or system of any of
the other tongue position stimulation embodiments elsewhere disclosed
herein, such as for example the numbered embodiments above or below,
further comprising providing a second stimulant to trigger an olfactory
response in the sleeping individual.

[0496] 310. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, where the
stimulant comprises a substance comprising at least one of a sour taste,
a citric taste, and a sweet taste.

[0497] 311. Another embodiment is the method, device, or system of any of
the other stimulant delivery embodiments elsewhere disclosed herein, such
as for example the numbered embodiments above or below, wherein the
stimulant comprises xylitol.

[0498] 312. Another embodiment is the method, device, or system of any of
the other controlled stimulant delivery embodiments elsewhere disclosed
herein, such as for example the numbered embodiments above or below,
wherein controlling the amount of stimulant comprises intermittently
pausing delivery of the stimulant comprises pausing the stimulant until a
triggering signal restarts delivery of the stimulant.

[0499] 313. Another embodiment is the embodiment 312, further comprising
using a dispensing unit in electrical communication with a sensor
assembly, wherein the triggering signal is generated in response to a
sensed parameter that is sensed by a sensor of the sensor assembly.

[0500] 314. Another embodiment is the method, device, or system of any of
the other sensor embodiments elsewhere disclosed herein, such as for
example the numbered embodiments above or below, wherein the sensor
comprises a pressure sensor, an optical sensor, a sound sensor, a
movement sensor, or an electro-magnetic sensor.

[0501] 315. Another embodiment is the method, device, or system of any of
the other sensor embodiments elsewhere disclosed herein, such as for
example the numbered embodiments above or below, wherein the sensor is
positioned in the mouth and generates a signal based on a movement or
position of the tongue.

[0502] 316. Another embodiment is the method, device, or system of any of
the other embodiments related to sensors, triggering signals, and
controlled delivery of stimulant as elsewhere disclosed herein, such as
for example the numbered embodiments above or below, wherein the amount
of stimulant delivered is determined by the triggering signal.

[0503] 317. Another embodiment is the method, device, or system of any of
the other embodiments related to sensors, triggering signals, and
controlled delivery of stimulant as elsewhere disclosed herein, such as
for example the numbered embodiments above or below, further comprising
measuring a degree of tongue movement with the sensor and using the
triggering signal to determine the amount of stimulant delivery based on
the degree of movement.

[0504] 318. Another embodiment is the method, device, or system of any of
the other embodiments related to sensors, triggering signals, and
controlled delivery of stimulant as elsewhere disclosed herein, such as
for example the numbered embodiments above or below, wherein controlling
delivery of the stimulant, including but not limited to intermittently
pausing delivery, are timed with an event or physiologic parameter
related to or comprising at least one of respiration, respiratory effect,
respiratory flow, hypoxia, hypopnea, oxygen saturation, pausing the
stimulant until a triggering signal restarts delivery of the stimulant.

[0505] 319. Another embodiment is the method, device, or system of any of
the other embodiments related to therapeutic agent delivery via a fluid
reservoir coupled to a dispensing port on an oral appliance, such as for
example the numbered embodiments above or below, wherein a valve is
provided which is located in a fluid path between the fluid reservoir and
the dispensing port, and wherein the valve is adjustable to allow for a
variable dispensing rate of the stimulant through the dispensing port.

[0506] 320. Another embodiment is the embodiment 319 above, wherein the
valve is adjustable to allow for intermittent change in the delivery,
such as for example but not limited to intermittently pausing delivery,
of the stimulant.

[0507] 321. Another embodiment is any one of the preceding system
embodiments above, to extent comprising a therapeutic agent provided on
or within the oral device for delivery to the mouth in the secured
configuration, and further comprising:

[0508] a coating deposited on a surface of the oral device at a delivery
location; wherein the therapy comprises a therapeutic agent contained
within the coating; and

[0509] wherein the coating is configured to release the therapeutic agent
into the mouth at the delivery location.

[0511] 323. Another embodiment is embodiment 321 above, and wherein the
coating is deposited onto the dispensing surface via a solvent-based
deposition.

[0512] 324. Another embodiment comprises the embodiment 321 above, and
further comprising a capsule or film over the coating and configured to
dissolve over sufficient time for the patient to fall asleep before the
therapeutic agent, such as a stimulant (such as a taste compound), starts
to release into the mouth.

[0514] 326. Another embodiment comprises the embodiment 325 above,
comprising multiple alternating layers of a coating comprising a taste
compound and tasteless transition layers so that intermittent delivery of
the taste is accomplished as the alternating layers dissolve.

[0515] 327. Another embodiment comprises any one of the preceding system
embodiments above, to extent comprising a therapeutic agent provided on
or within the oral device for delivery to the mouth in the secured
configuration, and further comprising a coating or capsule coupled to the
oral device and comprising multiple alternating dissolvable layers
configured for elevated and reduced delivery of therapeutic agent,
respectively.

[0517] 329. Another embodiment is any one of the preceding method
embodiments above, comprising containing a therapeutic agent on or within
the oral device for delivery to the mouth in the secured configuration,
and further comprising:

[0518] coupling the therapy to the oral device by depositing a therapeutic
agent in a surface coating on a dispensing surface of the oral device at
a delivery location; and

[0519] delivering the therapy into the mouth via the oral device by
releasing the therapeutic agent into the mouth via the surface coating at
the delivery location.

[0521] 331. Another embodiment is embodiment 329 above, and further
comprising depositing the coating onto the dispensing surface via a
solvent-based deposition.

[0522] 332. Another embodiment comprises the embodiment 329 above, and
further comprising a capsule or film deposited over the coating and
configured to dissolve in the mouth over sufficient time for the patient
to fall asleep before the therapeutic agent, such as a stimulant (such as
a taste compound), starts to release from the coating into the mouth.

[0523] 333. Another embodiment comprises the embodiment 332 above,
comprising sequentially dissolving multiple alternating layers of the
coating containing the therapeutic agent and the film, respectively, over
time so as to control agent delivery to change over time.

[0524] 334. Another embodiment comprises the embodiment 333 above,
comprising dissolving multiple alternating layers of the coating
comprising a taste compound and the film comprising tasteless transition
layers, so that intermittent delivery of the taste is accomplished as the
alternating layers dissolve.

[0525] 335. Another embodiment comprises any one of the preceding method
embodiments above and comprising providing a therapeutic agent on or
within the oral device for delivery to the mouth in the secured
configuration, and further comprising:

[0526] coupling a coating or capsule to the oral device and comprising
multiple alternating dissolvable layers; and

[0527] allowing the alternating dissolvable layers to dissolve
sequentially over time for elevated and reduced delivery of therapeutic
agent, respectively, over time.

[0530] dissolving the alternating layers sequentially over time allows
intermittent delivery of the therapeutic agent over time.

[0531] 337. Another embodiment is any one of the embodiments above and
comprising delivery of a therapeutic agent into the mouth via the oral
device, and wherein the therapeutic agent comprises a non-gas preparation
for delivery.

[0532] 338. Another embodiment is any one of the system embodiments above,
to extent related to delivering a therapy to an anterior portion of the
mouth, wherein the oral device in the secured configuration is configured
to isolate local delivery of the therapy at only an anterior location
within the mouth at or adjacent to the front incisors.

[0533] 339. Another embodiment is the system embodiment 338 above, used in
any one of the respective method embodiments above, wherein the method
further comprises locally delivering the therapy to only the anterior
portion of the mouth at or adjacent to the front incisors.

[0534] The above illustrations are examples of the invention described
herein. Because of the scope of the invention, it is specifically
contemplated that combinations of aspects of specific embodiments or
combinations of the specific embodiments themselves are within the scope
of this disclosure.

[0535] Although the description herein contains many details, these should
not be construed as limiting the scope of the invention but as merely
providing illustrations of some of the presently preferred embodiments of
this invention. Therefore, it will be appreciated that the scope of the
present invention fully encompasses other embodiments which may become
obvious to those skilled in the art. Furthermore, reference to an element
in the singular is not intended to mean "one and only one" unless
explicitly so stated, but rather "one or more." All structural, chemical,
and functional equivalents to the elements of the above-described
preferred embodiment that are known to those of ordinary skill in the art
are expressly incorporated herein by reference and are intended to be
encompassed by the present disclosure and claims. Moreover, it is not
necessary for a device or method to address each and every problem sought
to be solved by the present invention, for it to be encompassed by the
present disclosure and claims. Furthermore, no element, component, or
method step in the present disclosure is intended to be dedicated to the
public regardless of whether the element, component, or method step is
explicitly recited in the claims. No claim element herein is to be
construed under the provisions of 35 U.S.C. 112, sixth paragraph, unless
the element is expressly recited using the phrase "means for."